Роль иммунологического синапса в биологии хронического лимфолейкоза

Д.С. Бадмажапова, И.В. Гальцева, Е.Е. Звонков

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Дарима Сэмункоевна Бадмажапова, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(929)562-93-41; e-mail: badmazhapova-darima@mail.ru

Для цитирования: Бадмажапова Д.С., Гальцева И.В., Звонков Е.Е. Роль иммунологического синапса в биологии хронического лимфолейкоза. Клиническая онкогематология. 2018;11(4):313–8.

DOI: 10.21320/2500-2139-2018-11-4-313-318


РЕФЕРАТ

Хронический лимфолейкоз (ХЛЛ) — злокачественное лимфопролиферативное заболевание, которое проявляется накоплением опухолевых В-лимфоцитов с характерным иммунофенотипом (CD19+CD5+CD23+) в костном мозге, периферической крови и вторичных лимфоидных органах. По клиническому течению ХЛЛ является гетерогенным заболеванием. Это самый частый вид лейкоза у лиц старшей возрастной группы. Несмотря на применение новых лекарственных средств, остаются рефрактерные формы заболевания. Последние открытия в иммунологии позволили понять некоторые механизмы уклонения опухолевых клеток от иммунного надзора. Взаимодействие клеток иммунной системы друг с другом осуществляется за счет формирования иммунологического синапса, в котором основная роль отводится семейству молекул CD28/В7, так называемым иммунным контрольным точкам, регулирующим активационные и ингибирующие механизмы регуляции клеток. Приобретение клетками опухолевого фенотипа — многоступенчатый процесс, в котором клетка приобретает уникальные биологические свойства, в т. ч. и возможность быть невидимой для иммунитета. В отличие от солидных опухолей при лимфопролиферативных заболеваниях опухолевые В-лимфоциты способны экспрессировать главный комплекс гистосовместимости II класса и костимулирующие молекулы CD80 и CD86. Это свидетельствует о том, что они могут быть антигенпрезентирующими клетками для Т-клеток. Наличие коингибирующих молекул на поверхности опухолевых клеток может служить одним из факторов ингибирования иммунного ответа. В настоящем обзоре рассматриваются современные представления о биологических особенностях и иммунологических взаимодействиях клеток ХЛЛ с клетками микроокружения.

Ключевые слова: хронический лимфолейкоз, иммунологический синапс, иммунитет.

Получено: 15 марта 2018 г.

Принято в печать: 29 июня 2018 г.

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ЛИТЕРАТУРА

  1. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446–56. doi: 10.1182/blood-2007-06-093906.

  2. Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):v78–v84. doi: 10.1093/annonc/mdv303.

  3. The International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779–90. doi: 10.1016/S1470-2045(16)30029-8.

  4. Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8. doi: 10.1038/ni1102-991.

  5. Mellor AL, Munn DH. Tryptophan catabolism and regulation of adaptive immunity. J Immunol. 2003;170(12):5809–13. doi: 4049/jimmunol.170.12.5809.

  6. Vladimirova R, Popova D, Vikentieva E, et al. Chronic Lymphocytic Leukemia — Microenvironment and B Cells. In: Guenova M, Balatzenko G, eds. Leukemias: Updates and New Insights [Internet]; 2015. рр. 247–76. doi: 10.5772/60761. Available from: https://www.intechopen.com/books/leukemias-updates-and-new-insights/chronic-lymphocytic-leukemia-microenvironment-and-b-cells (accessed 31.05.2018).

  7. Ярилин А.А. Иммунология: учебник. M.: ГЭОТАР-Медиа, 2010. С. 394–403.

    [Yarilin AA. Immunologiya: uchebnik. (Immunology: a manual.) Moscow: GEOTAR-Media Publ.; 2010. pp. 394–403. (In Russ)]

  8. Kupfer A, Kupfer H. Imaging immune cell interactions and functions: SMACs and the immunological synapse. Semin Immunol. 2003;15(6):295–300. doi: 10.1016/j.smim.2003.09.001.

  9. Dustin ML. Modular design of immunological synapses and kinapses. Cold Spring Harb Perspect Biol. 2009;1(1):a002873. doi: 10.1101/cshperspect.a002873.

  10. Janeway C, Travers P, Walport M, et al. Immunobiology. The immune system in health and disease, 6th edn. Garland Science; 2005.

  11. Burger JA. Nurture versus nature: the microenvironment in chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2011;1:96–103. doi: 10.1182/asheducation-2011.1.96.

  12. Pasikowska M, Walsby E, Apollonio B, et al. Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration. 2016;128(4):563–73. doi: 10.1182/blood-2016-01-683128.

  13. Hofbauer JP, Heyder C, Denk U, et al. Development of CLL in the TCL1 transgenic mouse model is associated with severe skewing of the T-cell compartment homologous to human CLL. Leukemia. 2011;25(9):1452–8. doi: 10.1038/leu.2011.111.

  14. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23(1):515–48. doi:1146/annurev.immunol.23.021704.115611.

  15. Sansom DM. CD28, CTLA-4 and their ligands: who does what and to whom? 2000;101(2):169–77. doi: 10.1046/j.1365-2567.2000.00121.x.

  16. Boussiotis VA, Freeman GJ, Gribben GJ, et al. The role of B7-1/B7-2:CD28/CTLA-4 pathways in the prevention of anergy, induction of productive immunity and downregulated of the immune response. Immunol Rev. 1996;153(1):5–26. doi: 10.1111/j.1600-065x.1996.tb00918.x.

  17. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209(6):1201–17. doi: 10.1084/jem.20112741.

  18. Sheppard KA, Fitz LJ, Lee JM, et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3 zeta signalosome and downstream signaling to PKC theta. FEBS Lett. 2004;574(1–3):37–41. doi: 10.1016/j.febslet.2004.07.083.

  19. Thibult M-L, Mamessier E, Gertner-Dardenne J, et al. PD-1 is a novel regulator of human B-cell activation. Int Immunol. 2013;25(2):129–37. doi: 10.1093/intimm/dxs098.

  20. Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol. 2012;1(1):36. doi: 10.1186/2162-3619-1-36.

  21. Mills DM, Stolpa JC, Cambier JC. Modulation of MHC class II signal transduction by CD19. Adv Exp Med Biol. 2007;596:139–48. doi: 1007/0-387-46530-8_12.

  22. Kuijpers TW, Bende RJ, Baars PA, et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010;120(1):214–22. doi: 1172/JCI40231.

  23. Nitschke L. CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions. Immunol Rev. 2009;230(1):128–43. doi: 1111/j.1600-065X.2009.00801.x.

  24. Cerutti A, Kim EC, Shah S, et al. Dysregulation of CD30+ T cells by leukemia impairs isotype switching in normal B cells. Nat Immunol. 2001;2(2):150–6. doi: 10.1038/84254.

  25. Agata Y, Kawasaki A, Nishimura H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8(5):765–72. doi: 10.1093/intimm/8.5.765.

  26. Chinai JM, Janakiram M, Chen F, et al. New immunotherapies targeting the PD-1 pathway. Trends Pharmacol Sci. 2015;36(9):587–95. doi: 10.1016/j.tips.2015.06.005.

  27. Majolini MB, D’Elios MM, Galieni P, et al. Expression of the T-cell-specific tyrosine kinase Lck in normal B-1 cells and in chronic lymphocytic leukemia B cells. Blood. 1998;91(9):3390–6.

  28. Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008;118(7):2427–37. doi: 10.1172/JCI35017.

  29. Caligaris-Cappio F, Bertilaccio MT, Scielzo C. How the microenvironment wires the natural history of chronic lymphocytic leukemia. Semin Cancer Biol. 2014;24:43–8. doi: 10.1016/j.semcancer.2013.06.010.

  30. Damle RN, Calissano C, Chiorazzi N. Chronic lymphocytic leukaemia: a disease of activated monoclonal B cells. Clin Haematol. 2010;23(1):33–45. doi: 10.1016/j.beha.2010.02.001.

  31. Lauria F, Foa R, Catovsky D. Increase in T gamma lymphocytes in B-cell chronic lymphocytic leukaemia. Scand J Haematol. 1980;24(2):187–90. doi:1111/j.1600-0609.1980.tb02366.x.

  32. Herrmann F, Lochner A, Philippen H, et al. Imbalance of T cell subpopulations in patients with chronic lymphocytic leukaemia of the B cell type. Clin Exp Immunol. 1982;49(1):157–62.

  33. Mills KH, Worman CP, Cawley JC. T-cell subsets in B-chronic lymphocytic leukaemia (CLL). Br J Haematol. 1982;50(4):710–2. doi:1111/j.1365-2141.1982.tb01974.x.

  34. Platsoucas CD, Galinski M, Kempin S, et al. Abnormal T lymphocyte subpopulations in patients with B cell chronic lymphocytic leukemia: an analysis by monoclonal antibodies. J Immunol. 1982;129(5):2305–12.

  35. Pizzolo G, Chilosi M, Ambrosetti A, et al. Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia. Blood. 1983;62(6):1289–96.

  36. Ghia P, Strola G, Granziero L, et al. Chronic lymphocytic leukemia B cells are endowed with the capacity to attract CD4+, CD40L+ T cells by producing CCL22. Eur J Immunol. 2002;32(5):1403–13. doi: 10.1002/1521-4141(200205)32:5<1403::aid-immu1403>3.0.co;2-y.

  37. Bagnara D, Kaufman MS, Calissano C, et al. A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease. Blood. 2011;117(20):5463–72. doi: 10.1182/blood-2010-12-324210.

  38. Qorraj M, Bottcher M, Mougiakakos D. PD-L1/PD-1: new kid on the “immune metabolic” block. Oncotarget. 2017;8(43):73364–5. doi: 10.18632/oncotarget.20639.

  39. Burger JA, Tsukada N, Burger M, et al. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96(8):2655–63.

  40. Tsukada N, Burger JA, Zvaifler NJ, Kipps TJ. Distinctive features of “nurselike” cells that differentiate in the context of chronic lymphocytic leukemia. Blood. 2002;99(3):1030–7. doi: 10.1182/blood.V99.3.1030.

  41. Schiemann B, Gommerman JL, Vora K, et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001;293(5537):2111–4. doi: 1126/science.1061964.

  42. Schneider P, Takatsuka H, Wilson A, et al. Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen. J Exp Med. 2001;194(11):1691–7. doi: 10.1084/jem.194.11.1691.

  43. Mackay F, Schneider P, Rennert P, et al. BAFF and APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21(1):231–64. doi: 1146/annurev.immunol.21.120601.141152.

  44. Walton JA, Lydyard PM, Nathwani A, et al. Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4 perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype. Br J Haematol. 2010;148(2):274–84. doi: 10.1111/j.1365-2141.2009.07964.x.

  45. Nunes C, Wong R, Mason M, et al. Expansion of a CD8(+) PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clin Cancer Res. 2012;18(3):678–87. doi: 10.1158/1078-0432.CCR-11-2630.

  46. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170(3):1257–66. doi: 10.4049/jimmunol.170.3.1257.

  47. Ramsay AG, Clear AJ, Fatah R, et al. Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood. 2012;120(7):1412–21. doi: 10.1182/blood-2012-02-411678.

  48. Grzywnowicz M, Karabon L, Karczmarczyk A, et al. The function of a novel immunophenotype candidate molecule PD-1 in chronic lymphocytic leukemia. Leuk Lymphoma. 2015;56(10):2908–13. doi: 10.3109/10428194.2015.1017820.

  49. Li J, Pang N, Zhang Z, et al. PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi. 2017;38(03):198–203. doi: 10.3760/cma.j.issn.0253-2727.2017.03.005.

  50. Brusa D, Serra S, Coscia M, et al. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica. 2013;98(6):953–63. doi: 10.3324/haematol.2012.077537.

  51. Xerri L, Chetaille B, Seriari N, et al. Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Hum Pathol. 2008;39(7):1050–8. doi: 10.1016/j.humpath.2007.11.012.

  52. Panayiotidis P, Jones D, Ganeshaguru K, et al. Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. Br J Haematol. 1996;92(1):97–103. doi: 10.1046/j.1365-2141.1996.00305.x.

  53. Burger M, Hartmann T, Krome M, et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood. 2005;106(5):1824–30. doi: 10.1182/blood-2004-12-4918.

Ингибиторы иммунных контрольных точек в терапии лимфом

К.В. Лепик

НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой, ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова», ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022

Для переписки: Кирилл Викторович Лепик, ул. Льва Толстого, д. 6/8, Санкт-Петербург, Российская Федерация, 197022; e-mail: lepikkv@gmail.com

Для цитирования: Лепик К.В. Ингибиторы иммунных контрольных точек в терапии лимфом. Клиническая онкогематология. 2018;11(4):303–12.

DOI: 10.21320/2500-2139-2018-11-4-303-312


РЕФЕРАТ

Рецепторы и лиганды программируемой клеточной гибели (PD-1 и PD-L1) — наиболее изученные представители семейства иммунных контрольных точек (ИКТ), представляют собой ключевой элемент регуляции иммунного ответа. Способность злокачественных клеток воздействовать на рецепторы ИКТ является одним из важнейших механизмов подавления противоопухолевого иммунитета. Создание препаратов — ингибиторов ИКТ предоставляет возможность контроля и активации иммунного ответа, открывая новые перспективы иммунотерапии злокачественных новообразований, в т. ч. лимфом. В данном обзоре освещаются биологические основы применения ингибиторов ИКТ при классической лимфоме Ходжкина и неходжкинских лимфомах, а также представлен опыт их использования в клинике. Кроме того, обозначены новые подходы к созданию комбинированных режимов с включением ИКТ.

Ключевые слова: иммунные контрольные точки (ИКТ), PD-1, PD-L1, классическая лимфома Ходжкина, неходжкинские лимфомы, ингибиторы ИКТ.

Получено: 25 марта 2018 г.

Принято в печать: 23 июля 2018 г.

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ЛИТЕРАТУРА

  1. Walunas TL, Bakker CY, Bluestone JA. CTLA 4 ligation blocks CD28 dependent T cell activation. J Exp Med. 1996;183(6):2541–50.

  2. Freeman GJ, Long AJ, Iwai Y. Engagement of the Pd-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34. doi: 1084/jem.192.7.1027.

  3. Greaves P, Gribben JG. The role of B7 family molecules in hematologic malignancy. Blood. 2013;121(5):734–44. doi: 1182/blood-2012-10-385591.

  4. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311–9. doi: 1056/NEJMoa1411087.

  5. Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26(1):677–704. doi: 1146/annurev.immunol.26.021607.090331.

  6. Lee SJ, Jang BC, Lee SW, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006;580(3):755–62. doi: 1016/j.febslet.2005.12.093.

  7. Liu J, Hamrouni A, Wolowiec D, et al. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-gamma and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007;110(1):296–304. doi: 1182/blood-2006-10-051482.

  8. Fife BT, Pauken KE, Eagar TN, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 2009;10(11):1185–92. doi: 1038/ni.1790.

  9. Yokosuka T, Takamatsu M, Kobayashi-Imanishiet W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209(6):1201–17. doi: 1084/jem.20112741.

  10. Chemnitz JM, Parry RV, Nicholset KE, et al. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173(2):945–54. doi: 4049/jimmunol.173.2.945.

  11. Nurieva R, Thomas S, Nguyen T, et al. T-cell tolerance or function is determined by combinatorial costimulatory signals. EMBO J. 2006;25(11):2623–33. doi: 1038/sj.emboj.7601146.

  12. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7 H1 promotes T cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800. doi: 1038/nm730.

  13. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi: 1056/NEJMoa1003466.

  14. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. doi: 10.1056/NEJMoa1412082.

  15. Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA 4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375–84. doi: 1016/S1470-2045(15)70076-8.

  16. Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020–30. doi: 1200/JCO.2013.53.0105.

  17. Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34(23):2690–7. doi: 10.1200/jco.2016.66.4482.

  18. Carey CD, Gusenleitner D, Lipschitz M, et al. Topological analysis reveals a PD-L1-associated microenvironmental niche for Reed-Sternberg cells in Hodgkin lymphoma. Blood. 2017;130(22):2420–30. doi: 10.1182/blood-2017-03-770719.

  19. Kuppers R. The biology of Hodgkin’s lymphoma. Nat Rev Cancer. 2009;9(1):15–27. doi: 10.1038/nrc2542.

  20. Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17):3268–77. doi: 10.1182/blood-2010-05-282780.

  21. Chen BJ, Chapuy B, Ouyang J, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19(13):3462–73. doi: 10.1158/1078-0432.CCR-13-0855.

  22. Steidl C, Lee T, Shah SP, et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362(10):875–85. doi: 10.1056/NEJMoa0905680.

  23. Gordon SR, Maute RL, Dulken BW, et al. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017;545(7655):495–9. doi: 10.1038/nature22396.

  24. Paydas S, Bagir E, Seydaoglu G, et al. Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma. Ann Hematol. 2015;94(9):1545–52. doi: 10.1007/s00277-015-2403-2.

  25. Hollander P, Kamper P, Smedby KE, et al. High proportions of PD-1+ and PD-L1+ leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome. Blood Adv. 2017;1(18):1427–39. doi: 10.1182/bloodadvances.2017006346.

  26. Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17(9):1283–94. doi: 10.1016/S1470-2045(16)30167-X.

  27. Armand P, Shipp MA, Ribrag V, et al. Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study. Blood. 2016;128:1108, abstract.

  28. Armand P, Engert A, Younes A, et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018;36(14):1428–39. doi: 10.1200/JCO.2017.76.0793.

  29. Engert A, Fanale M, Santoro A, et al. Nivolumab for relapsed/refractory classical Hodgkin lymphoma after autologous transplant: full results after extended follow-up of the multicohort multicenter phase 2 CheckMate 205 trial. EHA conference 2017. Abstract S412.

  30. Armand P, Shipp MA, Ribrag V, et al. Programmed Death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol. 2016; 34(31):3733–9. doi: 10.1200/JCO.2016.67.3467.

  31. Chen R, Zinzani PL, Fanale MA, et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017;35(19):2125–32. doi: 10.1200/JCO.2016.72.1316.

  32. Tsimberidou AM, Braiteh F, Stewart DJ, Kurzrock R. Ultimate fate of oncology drugs approved by the US Food and Drug Administration without a randomized trial. J Clin Oncol. 2009;27(36):6243–50. doi: 10.1200/JCO.2009.23.6018.

  33. Nishijima TF, Shachar SS, Nyrop KA, Muss HB. Safety and tolerability of PD-1/PD-L1 inhibitors compared with chemotherapy in patients with advanced cancer: a meta-analysis. Oncologist. 2017;22(4):470–9. doi: 10.1634/theoncologist.2016-0419.

  34. Shi M, Roemer MGM, Chapuy B, et al. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol. 2014;38(12):1715–23. doi: 10.1097/PAS.0000000000000297.

  35. Twa DDW, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014;123(13):2062–5. doi: 10.1182/blood-2013-10-535443.

  36. Van Roosbroeck K, Ferreiro JF, Tousseyn T, et al. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies. Genes Chromos Cancer. 2016;55(5):428–41. doi: 10.1002/gcc.22345.

  37. Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017;130(3):267–70. doi: 10.1182/blood-2016-12-758383.

  38. Zinzani PL, Thieblemont C, Melnichenko V, et al. Efficacy and Safety of Pembrolizumab in Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma (rrPMBCL): Updated Analysis of the Keynote-170 Phase 2 Trial. ASH conference 2017. Abstract 2833B.

  39. Chapuy B, Roemer MGM, Stewart C, et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016;127(7):869–81. doi: 10.1182/blood-2015-10-673236.

  40. Nayak L, Iwamoto FM, LaCasce A, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3. doi: 10.1182/blood-2017-01-764209.

  41. Eberle FC, Salaverria I, Steidl C, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol. 2011;24(12):1586–97. doi: 10.1038/modpathol.2011.116.

  42. Melani C, Major A, Schowinsky J, et al. PD-1 blockade in mediastinal gray-zone lymphoma. N Engl J Med. 2017;377(1):89–91. doi: 10.1056/NEJMc1704767.

  43. Georgiou K, Chen L, Berglund M, et al. Genetic basis of PD-L1 overexpression in diffuse large B-cell lymphomas. Blood. 2016;127(24):3026–34. doi: 10.1182/blood-2015-12-686550.

  44. Kiyasu J, Miyoshi H, Hirata A, et al. Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood. 2015;126(19):2193–201. doi: 10.1182/blood-2015-02-629600.

  45. Chen M, Andreozzi M, Pockaj B, et al. Development and validation of a novel clinical fluorescence in situ hybridization assay to detect JAK2 and PD-L1 amplification. Mod Pathol. 2017;30(11):1516–26. doi: 10.1038/modpathol.2017.86.

  46. Gupta M, Han JJ, Stenson M, et al. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. Blood. 2012;119(12):2844–53. doi: 10.1182/blood-2011-10-388538.

  47. Choi JW, Kim Y, Lee JH, et al. MYD88 expression and L265P mutation in diffuse large B-cell lymphoma. Hum Pathol. 2013;44(7):1375–81. doi: 10.1016/j.humpath.2012.10.026.

  48. Bellucci R, Martin A, Bommarito D, et al. Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression. OncoImmunology. 2015;4(6):e1008824. doi: 10.1080/2162402X.2015.1008824.

  49. Laurent C, Charmpi K, Gravelle P, et al. Several immune escape patterns in non-Hodgkin’s lymphomas. OncoImmunology. 2015;4(8):e1026530. doi: 10.1080/2162402X.2015.1026530.

  50. Andorsky DJ, Yamada RE, Said J, et al. Programmed death ligand 1 is expressed by non-Hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011;17(13):4232–44. doi: 10.1158/1078-0432.CCR-10-2660.

  51. Jo JC, Kim M, Choi Y, et al. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2017;96(1):25–31. doi: 10.1007/s00277-016-2818-4.

  52. Muenst S, Hoeller S, Willi N, et al. Diagnostic and prognostic utility of PD-1 in B cell lymphomas. Dis Markers. 2010;29(1):47–53. doi: 10.1155/2010/404069.

  53. Hu L-Y, Xu X-L, Rao H-L, et al. Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study. Chin J Cancer. 2017;36(1):94. doi: 10.1186/s40880-017-0262-z.

  54. Ansell SM, Hurvitz SA, Koenig PA, et al. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2009;15(20):6446–53. doi: 10.1158/1078-0432.CCR-09-1339.

  55. Lesokhin AM, Ansell SM, Armand P, et al. Nivolumab in patients with relapsed or refractory hematologic malignancy: preliminary results of a phase Ib study. J Clin Oncol. 2016;34(23):2698–704. doi: 10.1200/JCO.2015.65.9789.

  56. Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199–206. doi: 10.1200/JCO.2012.48.3685.

  57. Palomba ML, Till BG, Park SI, et al. A phase IB study evaluating the safety and clinical activity of atezolizumab combined with obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma (NHL). Hematol Oncol. 2017;35(Suppl 2):137–8. doi: 10.1002/hon.2437_126.

  58. Ansell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic malignancies (CheckMate 039). Blood. 2016;128;22, abstract 183.

  59. Brusa D, Serra S, Coscia M, et al. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica. 2013;98(6):953–63. doi: 10.3324/haematol.2012.077537.

  60. Soma LA, Craig FE, Swerdlow SH. The proliferation center microenvironment and prognostic markers in chronic lymphocytic leukemia/small lymphocytic lymphoma. Hum Pathol. 2006;37(2):152–9. doi: 10.1016/j.humpath.2005.09.029.

  61. Nunes C, Wong R, Mason M, et al. Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clin Cancer Res. 2012;18(3):678–87. doi: 10.1158/1078-0432.CCR-11-2630.

  62. Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008;118(7):2427–37. doi: 10.1172/JCI35017.

  63. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–51. doi: 10.1158/1078-0432.ccr-07-4079.

  64. Ding W, LaPlant BR, Call TG, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017;129(26):3419–27. doi: 10.1182/blood-2017-02-765685.

  65. Panjwani P, Charu V, DeLisser M, et al. Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes. Hum Pathol. 2018;71:91–9. doi: 10.1016/j.humpath.2017.10.029.

  66. Menter T, Bodmer-Haecki A, Dirnhoferet S, et al. Evaluation of the diagnostic and prognostic value of PDL1 expression in Hodgkin and B-cell lymphomas. Hum Pathol. 2016;54:17–24. doi: 10.1016/j.humpath.2016.03.005.

  67. Wherry EJ. T cell exhaustion. Nat Immunol. 2011;131(6):492–9. doi: 10.1038/ni.2035.

  68. Wahlin BE, Aggarwal M, Montes-Moreno S, et al. A unifying microenvironment model in follicular lymphoma: outcome is predicted by programmed death-1—positive, regulatory, cytotoxic, and helper T cells and macrophages. Clin Cancer Res. 2010;16(2):637–50. doi: 10.1158/1078-0432.CCR-09-2487.

  69. Myklebust JH, Irish JM, Brody J, et al. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood. 2013;121(8):1367–76. doi: 10.1182/blood-2012-04-421826.

  70. Smeltzer JP, Jones JM, Ziesmer SC, et al. Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma. Clin Cancer Res. 2014;20(11):2862–72. doi: 10.1158/1078-0432.CCR-13-2367.

  71. Carreras J, Lopez-Guillermo A, Roncador G, et al. High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma. J Clin Oncol. 2009;27(9):1470–6. doi: 10.1200/JCO.2008.18.0513.

  72. Richendollar BG, Pohlman B, Elson P, et al. Follicular programmed death 1-positive lymphocytes in the tumor microenvironment are an independent prognostic factor in follicular lymphoma. Hum Pathol. 2011;42(4):552–7. doi: 10.1016/j.humpath.2010.08.015.

  73. Yang ZZ, Grote DM, Ziesmer SC, et al. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 2015;5:e281. doi: 10.1038/bcj.2015.1.

  74. Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med. 1984;311(23):1471–5. doi: 10.1056/NEJM198412063112303.

  75. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–51. doi: 10.1158/1078-0432.CCR-07-4079.

  76. Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. 2014;15(1):69–77. doi: 10.1016/S1470-2045(13)70551-5.

  77. Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin’s lymphoma. N Engl J Med. 2008;359(6):613–26. doi: 10.1056/NEJMra0708875.

  78. Nastoupil LJ, Westin J, Fowler N, et al. High response rates with pembrolizumab in combination with rituximab in patients with relapsed follicular lymphoma: interim results of an on open-label, phase II study. Hematol Oncol. 2017;35(Suppl 2):120–1. doi: 10.1002/hon.2437_108.

  79. Zaja F, Tabanelli V, Agostinelli C. CD38, BCL-2, PD-1, and PD-1L expression in nodal peripheral T-cell lymphoma: Possible biomarkers for novel targeted therapies? Am J Hematol. 2017;92(1):E1–E2. doi: 10.1002/ajh.24571.

  80. Xerri L, Chetaille B, Serriari N. Programmed death 1 is a marker of angioimmunoblastic T-cell lymphoma and B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia. Hum Pathol. 2008;39(7):1050–8. doi: 10.1016/j.humpath.2007.11.012.

  81. Wilcox RA, Feldman AL, Wada DA, et al. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood. 2009;114(10):2149–58. doi: 10.1182/blood-2009-04-216671.

  82. Vranic S, Ghosh N, Kimbrough J. PD-L1 Status in Refractory Lymphomas. PLoS One. 2016;11(11):e0166266. doi: 10.1371/journal.pone.0166266.

  83. Merryman RW, Armand P, Wright KT, Rodig SJ. Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma. Blood Adv. 2017;1(26):2643–54. doi: 10.1182/bloodadvances.2017012534.

  84. Marzec M, Zhang Q, Goradia A, et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci USA. 2008;105(52):20852–7. doi: 10.1073/pnas.0810958105.

  85. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol. 2003;170(3):1257–66. doi: 10.4049/jimmunol.170.3.1257.

  86. Hebart H, Lang P, Woessmann W. Nivolumab for Refractory Anaplastic Large Cell Lymphoma: A Case Report. Ann Intern Med. 2016;165(8):607–8. doi: 10.7326/116-0037.

  87. Cetinozman F, Jansen PM, Willemze R. Expression of programmed death-1 in primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma, cutaneous pseudo-T-cell lymphoma, and other types of cutaneous T-cell lymphoma. Am J Surg Pathol. 2012;36(1):109–16. doi: 10.1097/PAS.0b013e318230df87.

  88. Xia Y, Medeiros JL, Young KH. Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies. Biochim Biophys Acta. 2016;1865(1):58–71. doi: 10.1016/j.bbcan.2015.09.002.

  89. Cetinozman F, Jansen PM, Vermeer MH, et al. Differential expression of programmed death-1 (PD-1) in Sezary syndrome and mycosis fungoides. Arch Dermatol. 2012;148(12):1379. doi: 10.1001/archdermatol.2012.2089.

  90. Khodadoust M, Rook AH, Porcu P, et al. Pembrolizumab for treatment of relapsed/refractory mycosis fungoides and Sezary syndrome: clinical efficacy in a Citn multicenter phase 2 study. Blood. 2016;128:22, abstract 181.

  91. Kwong YL, Chan TSY, Tan D, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129(17):2437–42. doi: 10.1182/blood-2016-12-756841.

  92. Chan TSY, Li J, Loong F, et al. PD1 blockade with low-dose nivolumab in NK/T cell lymphoma failing L-asparaginase: efficacy and safety. Ann Hematol. 2018;97(1):193–6. doi: 10.1007/s00277-017-3127-2.

  93. Four M, Cacheux V, Tempier A, et al. PD1 and PDL1 expression in primary central nervous system diffuse large B-cell lymphoma are frequent and expression of PD1 predicts poor survival. Hematol Oncol. 2017;35(4):487–96. doi: 10.1002/hon.2375.

  94. Pelland K, Mathews S, Kamath A, et al. Dendritic Cell Markers and PD-L1 are Expressed in Mediastinal Gray Zone Lymphoma. Appl Immunohistochem Mol Morphol. 2017. doi: 10.1097/PAI.0000000000000615. [Epub ahead of print]

  95. Park JH, Han JH, Kanget HY, et al. Expression of follicular helper T-cell markers in primary cutaneous T-cell lymphoma. Am J Dermatopathol. 201;36(6):465–70. doi: 10.1097/DAD.0b013e3182a72f8c.

Теория и практика иммунотерапии, направленной против антигена PRAME

В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел.: +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Мисюрин В.А. Теория и практика иммунотерапии, направленной против антигена PRAME. Клиническая онкогематология. 2018;11(2):138-49.

DOI: 10.21320/2500-2139-2018-11-2-138-149


РЕФЕРАТ

Антиген PRAME, представляющий собой значимую мишень для моноклональных антител, является онкоспецифическим маркером, который активен на всех стадиях дифференцировки опухолевых клеток, и вызывает спонтанный T-клеточный ответ. Поскольку белок PRAME экспрессируется примерно у каждого второго больного с солидными опухолями и онкогематологическими заболеваниями, иммунотерапия против данного антигена имеет значительные перспективы. В настоящем обзоре обсуждается механизм развития спонтанного иммунного ответа против PRAME и роль данного антигена в иммунном надзоре. Рассматривается процесс развития PRAME-специфических T-клеток. Оцениваются риски применения иммунотерапии против PRAME-экспрессирующей клетки. Обсуждаются достоинства и недостатки различных подходов в иммунотерапии, в т. ч. использование дендритноклеточных вакцин, вакцинирование антигеном PRAME, выведение специфических T-клеток и разработка специфических моноклональных антител. Объяснены возможные причины неудач некоторых видов иммунотерапии, представлены пути их преодоления. Поиск литературы, на которой основан данный обзор, проводился в базах данных Pubmed, Scopus и eLibrary по ключевому слову «PRAME». Рассмотрены только те публикации, в которых изучались различные аспекты или создавались средства иммунотерапии, направленной против антигена PRAME.

Ключевые слова: PRAME, иммунотерапия, дендритноклеточные вакцины, пептидные вакцины, T-клеточные вакцины, терапевтические антитела.

Получено: 19 декабря 2017 г.

Принято в печать: 5 февраля 2018 г.

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ЛИТЕРАТУРА

  1. Lehmann F, Marchand M, Hainaut P, et al. Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. Eur J Immunol. 1995;25(2):340–7. doi: 10.1002/eji.1830250206.
  2. Ikeda H, Lethe B, Lehmann F, et al. Characterization of an Antigen That Is Recognized on a Melanoma Showing Partial HLA Loss by CTL Expressing an NK Inhibitory Receptor. Immunity. 1997;6(2):199–208. doi: 10.1016/s1074-7613(00)80426-4.
  3. Rezvani K, Yong AS, Tawab A, et al. Ex vivo characterization of polyclonal memory CD8 T-cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia. Blood. 2009;113(10):2245–55. doi: 10.1182/blood-2008-03-144071.
  4. Lutz M, Worschech A, Alb M, et al. Boost and loss of immune responses against tumor-associated antigens in the course of pregnancy as a model for allogeneic immunotherapy. Blood. 2015;125(2):261–72. doi: 10.1182/blood-2014-09-601302.
  5. LaVoy EC, Bollard CM, Hanley PJ, et al. A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults. Exerc Immunol Rev. 2015;21:144–53.
  6. Saldanha-Araujo F, Haddad R, Zanette DL, et al. Cancer/Testis Antigen Expression on Mesenchymal Stem Cells Isolated from Different Tissues. Anticancer Res. 2010;30(12):5023–7. doi: 10.1007/978-94-007-4798-2_11.
  7. Kirkin AF, Dzhandzhugazyan K, Zeuthen J. The Immunogenic Properties of Melanoma-Associated Antigens Recognized by Cytotoxic T Lymphocytes. Exp Clin Immunogenet. 1998;15(1):19–32. doi: 10.1159/000019050.
  8. Luetkens T, Schafhausen P, Uhlich F, et al. Expression, epigenetic regulation, and humoral immunogenicity of cancer-testis antigens in chronic myeloid leukemia. Leuk Res. 2010;34(12):1647–55. doi: 10.1016/j.leukres.2010.03.039.
  9. Luetkens T, Kobold S, Cao Y, et al. Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation. Cancer Immunol Immunother. 2014;63(11):1151–62. doi: 10.1007/s00262-014-1588-x.
  10. Kessler JH, Beekman NJ, Bres-Vloemans SA, et al. Efficient Identification of Novel HLA-A*0201–presented Cytotoxic T Lymphocyte Epitopes in the Widely Expressed Tumor Antigen PRAME by Proteasome-mediated Digestion Analysis. J Exp Med. 2001;193(1):73–88. doi: 10.1084/jem.193.1.73.
  11. Quintarelli C, Dotti G, Hasan ST, et al. High-avidity cytotoxic T lymphocytes specific for a new PRAME-derived peptide can target leukemic and leukemic-precursor cells. Blood. 2011;117(12):3353–62. doi: 10.1182/blood-2010-08-300376.
  12. Kessler JH, Mommaas B, Mutis T, et al. Competition-Based Cellular Peptide Binding Assays for 13 Prevalent HLA Class I Alleles Using Fluorescein-Labeled Synthetic Peptides. Hum Immunol. 2003;64(2):245–55. doi: 10.1016/S0198-8859(02)00787-5.
  13. Kawahara M, Hori T, Matsubara Y, et al. Identification of HLA class I–restricted tumor-associated antigens in adult T cell leukemia cells by mass spectrometric analysis. Exp Hematol. 2006;34(11):1496–504. doi: 10.1016/j.exphem.2006.06.010.
  14. Kessler JH, Khan S, Seifert U, et al. Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes. Nat Immunol. 2011;12(1):45–53. doi: 10.1038/ni.1974.
  15. Grunebach F, Mirakaj V, Mirakaj V, et al. BCR-ABL Is Not an Immunodominant Antigen in Chronic Myelogenous Leukemia. Cancer Res. 2006;66(11):5892–900. doi: 10.1158/0008-5472.CAN-05-2868.
  16. Greiner J, Schmitt M, Li L, et al. Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches. Blood. 2006;108(13):4109–17. doi: 10.1182/blood-2006-01-023127.
  17. Weber G, Caruana I, Rouce RH, et al. Generation of tumor antigen-specific T cell lines from pediatric patients with acute lymphoblastic leukemia – implications for immunotherapy. Clin Cancer Res. 2013;19(18):5079–91. doi: 10.1158/1078-0432.CCR-13-0955.
  18. Schneider V, Zhang L, Rojewski M, et al. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens. Int J Cancer. 2015;137(9):2083–92. doi: 10.1002/ijc.29583.
  19. Babiak A, Steinhauser M, Gotz M, et al. Frequent T cell responses against immunogenic targets in lung cancer patients for targeted immunotherapy. Oncol Rep. 2014;31(1):384–90. doi: 10.3892/or.2013.2804.
  20. Greiner J, Ringhoffer M, Simikopinko O, et al. Simultaneous expression of different immunogenic antigens in acute myeloid leukemia. Exp Hematol. 2000;28(12):1413–22. doi: 10.1016/S0301-472X(00)00550-6.
  21. Griffioen M, Kessler JH, Borghi M, et al. Detection and Functional Analysis of CD8+ T Cells Specific for PRAME: a Target for T-Cell Therapy. Clin Cancer Res. 2006;12(10):3130–6. doi: 10.1158/1078-0432.CCR-05-2578.
  22. Yao J, Caballero OL, Yung WK, et al. Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers. Cancer Immunol Res. 2014;2(4):371–9. doi: 10.1158/2326-6066.CIR-13-0088.
  23. Qin YZ, Zhu HH, Liu YR, et al. PRAME and WT1 transcripts constitute a good molecular marker combination for monitoring minimal residual disease in myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1442–9. doi: 10.3109/10428194.2012.743656.
  24. Gutierrez-Cosio S, de la Rica L, Ballestar E, et al. Epigenetic regulation of PRAME in acute myeloid leukemia is different compared to CD34+ cells from healthy donors: Effect of 5-AZA treatment. Leuk Res. 2012;36(7):895–9. doi: 10.1016/j.leukres.2012.02.030.
  25. Greiner J, Ringhoffer M, Taniguchi M, et al. mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies. Int J Cancer. 2004;108(5):704–11. doi: 10.1002/ijc.11623.
  26. Paydas S, Tanriverdi K, Yavuz S, et al. PRAME mRNA Levels in Cases With Acute Leukemia: Clinical Importance and Future Prospects. Am J Hematol. 2005;79(4):257–61.
  27. Gerber JM, Qin L, Kowalski J, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86(1):31–7. doi: 10.1002/ajh.21915.
  28. Yong AS, Keyvanfar K, Eniafe R, et al. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy. Leukemia. 2008;22(9):1721–7. doi: 10.1038/leu.2008.161.
  29. Steger B, Milosevic S, Doessinger G, et al. CD4+ and CD8+ T-cell reactions against leukemia-associated- or minor-histocompatibility-antigens in AML-patients after allogeneic SCT. Immunobiology. 2014;219(4):247–60. doi: 10.1016/j.imbio.2013.10.008.
  30. Doolan P, Clynes M, Kennedy S, et al. Prevalence and prognostic and predictive relevance of PRAME in breast cancer. Breast Cancer Res Treat. 2008;109(2):359–65. doi: 10.1007/s10549-007-9643-3.
  31. Altvater B, Kailayangiri S, Theimann N, et al. Common Ewing sarcoma-associated antigens fail to induce natural T cell responses in both patients and healthy individual. Cancer Immunol Immunother. 2014;63(10):1047–60. doi: 10.1007/s00262-014-1574-3.
  32. Hughes A, Clarson J, Tang C, et al. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017;129(9):1166–1176. doi: 10.1182/blood-2016-10-745992.
  33. Schmitt M, Li L, Giannopoulos K, et al. Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. Exp Hematol. 2006;34(12):1709–19. doi: 10.1016/j.exphem.2006.07.009.
  34. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8(1):59–73. doi: 10.1038/nri2216.
  35. Morandi F, Chiesa S, Bocca P, et al. Tumor mRNA–Transfected Dendritic Cells Stimulate the Generation of CTL That Recognize Neuroblastoma-Associated Antigens and Kill Tumor Cells: Immunotherapeutic Implications. Neoplasia. 2006;8(10):833–42. doi: 10.1593/neo.06415.
  36. Winkler C, Steingrube DS, Altermann W, et al. Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses. Cancer Immunol Immunother. 2012;61(10):1769–79. doi: 10.1007/s00262-012-1239-z.
  37. Gerdemann U, Katari U, Christin AS, et al. Cytotoxic T Lymphocytes Simultaneously Targeting Multiple Tumor-associated Antigens to Treat EBV Negative Lymphoma. Mol Ther. 2011;19(12):2258–68. doi: 10.1038/mt.2011.167.
  38. Mohamed YS, Bashawri LA, Vatte C, et al. The in vitro generation of multi-tumor antigen-specific cytotoxic T cell clones: Candidates for leukemia adoptive immunotherapy following allogeneic stem cell transplantation. Mol Immunol. 2016;77:79–88. doi: 10.1016/j.molimm.2016.07.012.
  39. Li L, Schmitt A, Reinhardt P, et al. Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia. Cancer Immun. 2003;3:8.
  40. Li L, Reinhardt P, Schmitt A, et al. Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens. Cancer Immunol Immunother. 2005;54(7):685–93. doi: 10.1007/s00262-004-0631-8.
  41. Li L, Giannopoulos K, Reinhardt P, et al. Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Int J Oncol. 2006;28(4):855–61. doi: 10.3892/ijo.28.4.855.
  42. Altvater B, Pscherer S, Landmeier S, et al. Activated human γδ T cells induce peptide-specific CD8+ T-cell responses to tumor-associated self-antigens. Cancer Immunol Immunother. 2012;61(3):385–96. doi: 10.1007/s00262-011-1111-6.
  43. Matsushita M, Ikeda H, Kizaki M, et al. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001;112(4):916–26. doi: 10.1046/j.1365-2141.2001.02670.x.
  44. van den Ancker W, Ruben JM, Westers TM, et al. Priming of PRAME- and WT1-specific CD8+ T cells in healthy donors but not in AML patients in complete remission. Oncoimmunology. 2013;2(4):e23971. doi: 10.4161/onci.23971.
  45. Yao Y, Zhou J, Wang L, et al. Increased PRAME-Specific CTL Killing of Acute Myeloid Leukemia Cells by Either a Novel Histone Deacetylase Inhibitor Chidamide Alone or Combined Treatment with Decitabine. PLoS One. 2013;8(8):e70522. doi: 10.1371/journal.pone.0070522.
  46. Zhang M, Graor H, Visioni A, et al. T Cells Derived From Human Melanoma Draining Lymph Nodes Mediate Melanoma-specific Antitumor Responses In Vitro and In Vivo in Human Melanoma Xenograft Model. J Immunother. 2015;38(6):229–38. doi: 10.1097/CJI.0000000000000078.
  47. Yan M, Himoudi N, Basu BP, et al. Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-20-Deoxycytidine. Cancer Immunol Immunother. 2011;60(9):1243–55. doi: 10.1007/s00262-011-1024-4.
  48. Quintarelli C, Dotti G, De Angelis B, et al. Cytotoxic T lymphocytes directed to the preferentially expressed antigen of melanoma (PRAME) target chronic myeloid leukemia. Blood. 2008;112(5):1876–85. doi: 10.1182/blood-2008-04-150045.
  49. Amir AL, van der Steen DM, van Loenen MM, et al. PRAME-Specific Allo-HLA–Restricted T Cells with Potent Antitumor Reactivity Useful for Therapeutic T-Cell Receptor Gene Transfer. Clin Cancer Res. 2011;17(17):5615–25. doi: 10.1158/1078-0432.CCR-11-1066.
  50. van Loenen MM, de Boer R, Hagedoorn RS, et al. Multi-cistronic vector encoding optimized safety switch for adoptive therapy with T-cell receptor-modified T cells. Gene Ther. 2013;20(8):861–7. doi: 10.1038/gt.2013.4.
  51. Spel L, Boelens JJ, van der Steen DM, et al. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma. Oncotarget. 2015;6(34):35770–81. doi: 10.18632/oncotarget.5657.
  52. Weber JS, Vogelzang NJ, Ernstoff MS, et al. A Phase 1 Study of a Vaccine Targeting Preferentially Expressed Antigen in Melanoma and Prostate-specific Membrane Antigen in Patients With Advanced Solid Tumors. J Immunother. 2011;34(7):556–67. doi: 10.1097/CJI.0b013e3182280db1.
  53. Garcon N, Silvano J, Kuper CF, et al. Non-clinical safety evaluation of repeated intramuscular administration of the AS15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys. J Appl Toxicol. 2016;36(2):238–56. doi: 10.1002/jat.3167.
  54. Gerard C, Baudson N, Ory T, et al. A Comprehensive Preclinical Model Evaluating the Recombinant PRAME Antigen Combined With the AS15 Immunostimulant to Fight Against PRAME-expressing Tumors. J Immunother. 2015;38(8):311–20. doi: 10.1097/CJI.0000000000000095.
  55. Pujol JL, De Pas T, Rittmeyer A, et al. Safety and Immunogenicity of the PRAME Cancer Immunotherapeutic in Patients with Resected Non–Small Cell Lung Cancer: A Phase I Dose Escalation Study. J Thorac Oncol. 2016;11(12):2208–17. doi: 10.1016/j.jtho.2016.08.120.
  56. Gutzmer R, Rivoltini L, Levchenko E, et al. Safety and immunogenicity of the PRAME cancer immunotherapeutic in metastatic melanoma: results of a phase I dose escalation study. ESMO Open. 2016;1(4):e000068.
  57. Blais N, Martin D, Palmantier RM. Vaccin. Patent PCT/EP2008/050290. Available from: https://patentscope.wipo.int/search/ru/detail.jsf?docId=WO2008087102&redirectedID=true. (accessed 08.12.2017).
  58. Chang AY, Dao T, Gejman RS, et al. A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I antigens. J Clin Invest. 2017;127(7):2705–18. doi: 10.1172/JCI92335.
  59. Pankov D, Sjostrom L, Kalidindi T, et al. In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME). Oncotarget. 2017;8(39):65917–31. doi: 10.18632/oncotarget.19579.
  60. Финашутина Ю.П., Мисюрин А.В., Ахлынина Т.В. и др. Получение рекомбинантного раково-тестикулярного белка PRAME и моноклональных антител к нему. Российский биотерапевтический журнал. 2015;14(3):29–36.[Finashutina YuP, Misyurin AV, Akhlynina TV, et al. Production of recombinant PRAME cancer testis antigen and its specific monoclonal antibodies. Rossiiskii bioterapevticheskii zhurnal. 2015;14(3):29–36. (In Russ)]
  61. Мисюрин А.В., Финашутина Ю.П. Антигенная композиция и ее терапевтическое применение для профилактики и лечения онкологических заболеваний, рекомбинантная плазмидная ДНК, обеспечивающая синтез гибридного белка, а также способ получения белка. Патент РФ на изобретение № 2590701/13.04.29. Бюл. № 19. Доступно по: http://www.fips.ru/cdfi/fips.dll/en?ty=29&docid=2590701. Ссылка активна на 08.12.2017.[Misyurin AV, Finashutina YuP. Antigennaya kompozitsiya i ee terapevticheskoe primenenie dlya profilaktiki i lecheniya onkologicheskikh zabolevanii, rekombinantnaya plazmidnaya DNK, obespechivayushchaya sintez gibridnogo belka, a takzhe sposob polucheniya belka. Patent RUS No. 2590701/13.04.29. Byul. No. 19. Available from: http://www.fips.ru/cdfi/fips.dll/en?ty=29&docid=2590701. (accessed 08.12.2017) (In Russ)]
  62. Лыжко Н.А., Ахлынина Т.В., Мисюрин А.В. и др. Повышение уровня экспрессии гена PRAME в опухолевых клетках сопровождается локализацией белка в клеточном ядре. Российский биотерапевтический журнал. 2015;14(4):19–30.[Lyzhko NA, Ahlynina TV, Misyurin AV, et al. The increased PRAME expression in cancer cells is associated with deposit of the protein in cell nucleus. Rossiiskii bioterapevticheskii zhurnal. 2015;14(4):19–30. (In Russ)]
  63. Лыжко Н.А., Мисюрин В.А., Финашутина Ю.П. и др. Проявление цитостатического эффекта моноклональных антител к белку PRAME. Российский биотерапевтический журнал. 2016;15(4):53–8. doi: 10.17650/1726-9784-2016-15-4-53-58.[Lyzhko NA, Misyurin VA, Finashutina YuP, et al. Development of cytostatic effect of monoclonal antibodies to the protein PRAME. Rossiiskii bioterapevticheskii zhurnal. 2016;15(4):53–8. doi: 10.17650/1726-9784-2016-15-4-53-58. (In Russ)]
  64. Dillman RO. Cancer immunotherapy. Cancer Biother Radiopharm 2011;26:1–64. doi: 10.1089/cbr.2010.0902.
  65. Theisen D, Murphy K. The role of cDC1s in vivo: CD8 T cell priming through cross-presentation. F1000Res. 2017;6:98. doi: 10.12688/f1000research.9997.1.
  66. Epping MT, Wang L, Edel MJ, et al. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122(6):835–47. doi: 10.1016/j.cell.2005.07.003.
  67. De Carvalho DD, Mello BP, Pereira WO, Amarante-Mendes GP. PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy. Curr Mil Med. 2013;13(2):296–304. doi: 10.2174/1566524011313020006.
  68. Мисюрин В.А. Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях. Клиническая онкогематология. 2018;11(1):26–33. doi: 10.21320/2500-2139-2018-11-1-26-33. [Misyurin VA. Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases. Clinical oncohematology

Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях

В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Москва, Каширское ш., д. 24, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел. +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Мисюрин В.А. Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях. Клиническая онкогематология. 2018;11(1):26–33.

DOI: 10.21320/2500-2139-2018-11-1-26-33


РЕФЕРАТ

Хотя и активность PRAME была впервые установлена при солидных опухолях, данный ген чрезвычайно часто экспрессируется при онкогематологических заболеваниях. Ген PRAME может быть использован как надежный биомаркер наличия опухолевых клеток. Определение транскриптов PRAME используется при мониторинге минимальной остаточной болезни и диагностике молекулярного рецидива. При проведении экспериментов с PRAME-экспрессирующими линиями лейкозных клеток получены противоречивые результаты. По этой причине объяснить наблюдаемое влияние экспрессии PRAME на прогноз очень сложно. Тем не менее при хронических миелопролиферативных заболеваниях и хроническом миелоидном лейкозе активность PRAME связана с худшим прогнозом, а при острых лейкозах лимфоидной и миелоидной направленности — с лучшим. Несмотря на большой объем клинических наблюдений, при некоторых нозологических формах влияние экспрессии PRAME на прогноз остается неизвестным. В настоящем обзоре литературы широко представлены известные данные об экспрессии гена PRAME при онкогематологических заболеваниях.

Ключевые слова: PRAME, лейкозы, лимфомы, прогноз.

Получено: 14 сентября 2017 г.

Принято в печать: 2 декабря 2017 г.

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ЛИТЕРАТУРА

  1. Ikeda H, Lethe B, Lehmann F, et al. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity. 1997;6(2):199–208. doi: 10.1016/S1074-7613(00)80426-4.
  2. Greiner J, Ringhoffer M, Simikopinko O, et al. Simultaneous expression of different immunogenic antigens in acute myeloid leukemia. Exp Hematol. 2000;28(12):1413–22. doi: 10.1016/S0301-472X(00)00550-6.
  3. Epping MT, Wang L, Edel MJ, et al. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122(6):835–47. doi: 10.1016/j.cell.2005.07.003.
  4. De Carvalho DD, Mello BP, Pereira WO, Amarante-Mendes GP. PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy. Curr Mol Med. 2013;13(2):296–304. doi: 10.2174/156652413804810727.
  5. Costessi A, Mahrour N, Tijchon E, et al. The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters. EMBO J. 2011;30(18):3786–98. doi: 10.1038/emboj.2011.262.
  6. Kim HL, Seo YR. Molecular and genomic approach for understanding the gene-environment interaction between Nrf2 deficiency and carcinogenic nickel-induced DNA damage. Oncol Rep. 2012;28(6):1959–67. doi: 10.3892/or.2012.2057.
  7. Yao J, Caballero OL, Yung WK, et al. Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers. Cancer Immunol Res. 2014;2(4):371–9. doi: 10.1158/2326-6066.CIR-13-0088.
  8. van Baren N, Chambost H, Ferrant A, et al. PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Br J Haematol. 1998;102(5):1376–9. doi: 10.1046/j.1365-2141.1998.00982.x.
  9. Oehler VG, Guthrie KA, Cummings CL, et al. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. Blood. 2009;114(15):3299–308. doi: 10.1182/blood-2008-07-170282.
  10. Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Epigenetic regulation of PRAME gene in chronic myeloid leukemia. Leuk Res. 2007;31(11):1521–8. doi: 10.1016/j.leukres.2007.02.016.
  11. Ortmann CA, Eisele L, Nuckel H, et al. Aberrant hypomethylation of the cancer–testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia. Ann Hematol. 2008;87(10):809–18. doi: 10.1007/s00277-008-0514-8.
  12. Gutierrez-Cosio S, de la Rica L, Ballestar E, et al. Epigenetic regulation of PRAME in acute myeloid leukemia is different compared to CD34+ cells from healthy donors: Effect of 5-AZA treatment. Leuk Res. 2012;36(7):895–9. doi: 10.1016/j.leukres.2012.02.030.
  13. Arons E, Suntum T, Margulies I, et al. PRAME expression in Hairy Cell Leukemia. Leuk Res. 2008;32(9):1400–6. doi: 10.1016/j.leukres.2007.12.010.
  14. Steinbach D, Schramm A, Eggert A, et al. Identification of a Set of Seven Genes for the Monitoring of Minimal Residual Disease in Pediatric Acute Myeloid Leukemia. Clin Cancer Res. 2006;12(8):2434–41. doi: 10.1158/1078-0432.CCR-05-2552.
  15. Matsushita M, Ikeda H, Kizaki M, et al. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001;112(4):916–26. doi: 10.1046/j.1365-2141.2001.02670.x.
  16. Tajeddine N, Millard I, Gailly P, Gala JL. Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia. Clin Chem Lab Med. 2006;44(5):548–55. doi: 10.1515/CCLM.2006.106.
  17. Schneider V, Zhang L, Rojewski M, et al. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens. Int J Cancer. 2015;137(9):2083–92. doi: 10.1002/ijc.29583.
  18. Гапонова Т.В., Менделеева Л.П., Мисюрин А.В. и др. Экспрессия опухолеассоциированных генов PRAME, WT1 и XIAP у больных множественной миеломой. Онкогематология. 2009;2:52–7. [Gaponova TV, Mendeleeva LP, Misyurin AV, et al. Expression of PRAME, WT1 and XIAP tumor-associated genes in patients with multiple myeloma. Onkogematologiya. 2009;2:52–7. (In Russ)]
  19. Абраменко И.В., Белоус Н.И., Крячок И.А. и др. Экспрессия гена PRAME при множественной миеломе. Терапевтический архив. 2004;74(7):77–81. [Abramenko IV, Belous NI, Kryachok IA, et al. Expression of PRAME gene in multiple myeloma. Terapevticheskii arkhiv. 2004;74(7):77–81. (In Russ)]
  20. Мисюрин В.А., Мисюрин А.В., Кесаева Л.А. и др. Новые маркеры прогрессирования хронического миелолейкоза. Клиническая онкогематология. 2014;7(2):206–12. [Misyurin VA, Misyurin AV, Kesayeva LA, et al. New molecular markers of CML progression. Klinicheskaya onkogematologiya. 2014;7(2):206–12. (In Russ)]
  21. van Baren N, Brasseur F, Godelaine D, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood. 1999;94(4):1156–64.
  22. Pellat-Deceunynck C, Mellerin M., Labarriere N, et al. The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells. Eur J Immunol. 2000;30(3):803–9. doi: 10.1002/1521-4141(200003)30:3<803:AID-IMMU803>3.0.CO;2-P.
  23. Andrade VC, Vettore AL, Felix RS, et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008;8:2.
  24. Qin Y, Lu J, Bao L, et al. Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma. Chin Med J (Engl). 2014;127(9):1666–71. doi: 10.3760/cma.j.issn.0366-6999.20132356.
  25. Proto-Siqueira R, Falcao RP, de Souza CA, et al. The expression of PRAME in chronic lymphoproliferative disorders. Leuk Res. 2003;27(5):393–6. doi: 10.1016/S0145-2126(02)00217-5.
  26. Proto-Siqueira R, Figueiredo-Pontes LL, Panepucci RA, et al. PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. Leuk Res. 2006;30(11):1333–39. doi: 10.1016/j.leukres.2006.02.031.
  27. Paydas S, Tanriverdi K, Yavuz S, Seydaoglu G. PRAME mRNA levels in cases with chronic leukemia: Clinical importance and review of the literature. Leuk Res. 2007;31(3):365–9. doi: 10.1016/j.leukres.2006.06.022.
  28. Kawano R, Karube K, Kikuchi M, et al. Oncogene associated cDNA microarray analysis shows PRAME gene expression is a marker for response to anthracycline containing chemotherapy in patients with diffuse large B-cell lymphoma. J Clin Exp Hematop. 2009;49(1):1–7. doi: 10.3960/jslrt.49.1.
  29. Mitsuhashi K, Masuda A, Wang YH, et al. Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy. Int J Hematol. 2014;100(1):88–95. doi: 10.1007/s12185-014-1593-z.
  30. Schmitt M, Li L, Giannopoulos K, et al. Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. Exp Hematol. 2006;34(12):1709–19. doi: 10.1016/j.exphem.2006.07.009.
  31. Qian J, Zhu Z.H, Lin J, et al. Hypomethylation of PRAME promoter is associated with poor prognosis in myelodysplastic syndrome. Br J Haematol. 2011;154(1):153–5. doi: 10.1111/j.1365-2141.2011.08585.x.
  32. Ding K, Wang XM, Fu R, et al. PRAME Gene Expression in Acute Leukemia and Its Clinical Significance. Cancer Biol Med. 2012;9(1):73–6. doi: 10.3969/j.issn.2095-3941.2012.01.013.
  33. Greiner J, Ringhoffer M, Taniguchi M, et al. mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies. Int J Cancer. 2004;108(5):704–11. doi: 10.1002/ijc.11623.
  34. Li L, Reinhardt P, Schmitt A, et al. Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens. Cancer Immunol Immunother. 2005;54(7):685–93. doi: 10.1007/s00262-004-0631-8.
  35. Atanackovic D, Luetkens T, Kloth B, et al. Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia. Am J Hematol. 2011;86(11):918–22. doi: 10.1002/ajh.22141.
  36. Gerber JM, Qin L, Kowalski J, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86(1):31–7. doi: 10.1002/ajh.21915.
  37. Qin YZ, Zhu HH, Liu YR, et al. PRAME and WT1 transcripts constitute a good molecular marker combination for monitoring minimal residual disease in myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1442–9. doi: 10.3109/10428194.2012.743656.
  38. Steinbach D, Viehmann S, Zintl F, Gruhn B. PRAME gene expression in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2002;138(1):89–91. doi: 10.1016/S0165-4608(02)00582-4.
  39. Steinbach D, Hermann J, Viehmann S, et al. Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet. 2002;133(2):118–23. doi: 10.1016/S0165-4608(01)00570-2.
  40. Spanaki A, Perdikogianni C, Linardakis E, Kalmanti M. Quantitative assessment of PRAME expression in diagnosis of childhood acute leukemia. Leuk Res. 2007;31(5):639–42. doi: 10.1016/j.leukres.2006.06.006.
  41. Steinbach D, Bader P, Willasch A, et al. Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia. Clin Cancer Res. 2015;21(6):1353–9. doi: 10.1158/1078-0432.CCR-14-1999.
  42. Paydas S, Tanriverdi K, Yavuz S, et al. PRAME mRNA levels in cases with chronic leukemia: Clinical Importance and Future Prospects. Am J Hematol. 2005;79(4):257–61. doi: 10.1002/ajh.20425.
  43. Steinbach D, Pfaffendorf N, Wittig S, Gruhn B. PRAME expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia. Cancer Genet Cytogenet. 2007;177(1):51–4. doi: 10.1016/j.cancergencyto.2007.05.011.
  44. Santamaria C, Chillon MC, Garcia-Sanz R, et al. The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia. Haematologica. 2008;93(12):1797–805. doi: 10.3324/haematol.13214.
  45. Qin Y, Zhu H, Jiang B, et al. Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. Leuk Res. 2009;33(3):384–90. doi: 10.1016/j.leukres.2008.08.026.
  46. Мисюрин В.А., Лукина А.Е., Мисюрин А.В. и др. Особенности соотношения уровней экспрессии генов PRAME и PML/RARa в дебюте острого промиелоцитарного лейкоза. Российский биотерапевтический журнал. 2014;13(1):9–16. [Misyurin VA, Lukina AE, Misyurin AV, et al. A ratio between gene expression levels of PRAME and PML/RARA at the onset of acute promyelocytic leukemia and clinical features of the disease. Rossiiskii bioterapevticheskii zhurnal. 2014;13(1):9–16. (In Russ)]
  47. Liberante FG, Pellagatti A, Boncheva V, et al. High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation. Br J Haematol. 2013;162(2):282–5. doi: 10.1111/bjh.12352.
  48. Goellner S, Steinbach D, Schenk T, et al. Childhood acute myelogenous leukaemia: Association between PRAME, apoptosis- and MDR-related gene expression. Eur J Cancer. 2006;42(16):2807–14. doi: 10.1016/j.ejca.2006.06.018.
  49. Tajeddine N, Louis M, Vermylen C, et al. Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo. Leuk Lymphoma. 2008;49(6):1123–31. doi: 10.1080/10428190802035933.
  50. Santamaria CM, Chillon MC, Garcia-Sanz R, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia. Blood. 2009;114(1):148–52. doi: 10.1182/blood-2008-11-187724.
  51. Ercolak V, Paydas S, Bagir E, et al. PRAME Expression and Its Clinical Relevance in Hodgkin’s Lymphoma. Acta Haematol. 2015;134(4):199–207. doi: 10.1159/000381533.
  52. Luetkens T, Kobold S, Cao Y, et al. Functional autoantibodies against SSX‐2 and NY‐ESO‐1 in multiple myeloma patients after allogeneic stem cell transplantation. Cancer Immunol Immunother. 2014;63(11):1151–62. doi: 10.1007/s00262-014-1588-x.
  53. Gunn SR, Bolla AR, Barron LL, et al. Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene. Leuk Res. 2009;33(9):1276–81. doi: 10.1016/j.leukres.2008.10.010.
  54. Mraz M, Stano Kozubik K, Plevova K, et al. The origin of deletion 22q11 in chronic lymphocytic leukemia is related to the rearrangement of immunoglobulin lambda light chain locus. Leuk Res. 2013;37(7):802–8. doi: 10.1016/j.leukres.2013.03.018.
  55. Staege MS, Banning-Eichenseer U, Weissflog G, et al. Gene expression profiles of Hodgkin’s lymphoma cell lines with different sensitivity to cytotoxic drugs. Exp Hematol. 2008;36(7):886–96. doi: 10.1016/j.exphem.2008.02.014.
  56. Kewitz S, Staege MS. Knock-Down of PRAME Increases Retinoic Acid Signaling and Cytotoxic Drug Sensitivity of Hodgkin Lymphoma Cells. PLoS One. 2013;8(2):e55897. doi: 10.1371/journal.pone.0055897.
  57. Bea S, Salaverria I, Armengol L, et al. Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling. Blood. 2009;113(13):3059–69. doi: 10.1182/blood-2008-07-170183.
  58. Liggins AP, Lim SH, Soilleux EJ, et al. A panel of cancer-testis genes exhibiting broadspectrum expression in haematological malignancies. Cancer Immun. 2010;10:8.
  59. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103(8):2794–9. doi: 10.1073/pnas.0510423103.
  60. Luetkens T, Schafhausen P, Uhlich F, et al. Expression, epigenetic regulation, and humoral immunogenicity of cancer-testis antigens in chronic myeloid leukemia. Leuk Res. 2010;34(12):1647–55. doi: 10.1016/j.leukres.2010.03.039.
  61. Hughes A, Clarson J, Tang C, et al. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017;129(9):1166–76. doi: 10.1182/blood-2016-10-745992.
  62. Khateeb EE, Morgan D. Preferentially Expressed Antigen of Melanoma (PRAME) and Wilms’ Tumor 1 (WT 1) Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival. Open Access Maced J Med Sci. 2015;3(1):57–62. doi: 10.3889/oamjms.2015.001.
  63. Zhang YH, Lu AD, Yang L, et al. PRAME overexpression predicted good outcome in pediatric B-cell acute lymphoblastic leukemia patients receiving chemotherapy. Leuk Res. 2017;52):43–9. doi: 10.1016/j.leukres.2016.11.005.
  64. McElwaine S, Mulligan C, Groet J, et al. Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down’s syndrome, revealing PRAME as a specific discriminating marker. Br J Haematol. 2004;125(6):729–42. doi: 10.1111/j.1365-2141.2004.04982.x.
  65. Tanaka N, Wang YH, Shiseki M, et al. Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells. Leuk Res. 2011;35(9):1219–25. doi: 10.1016/j.leukres.2011.04.005.
  66. De Carvalho D.D, Binato R, Pereira W.O, et al. BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients. Oncogene. 2011;30(2):223–33. doi: 10.1038/onc.2010.409.
  67. Tajeddine N, Gala JL, Louis M, et al. Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase-independent cell death in vitro and reduces tumorigenicity in vivo. Cancer Res. 2005;65(16):7348–55. doi: 10.1158/0008-5472.CAN-04-4011.
  68. Yan H, Zhao RM, Wang ZJ, et al. Knockdown of PRAME enhances adriamycin-induced apoptosis in chronic myeloid leukemia cells. Eur Rev Med Pharmacol Sci. 2015;19(24):4827–34. doi: 10.18632/oncotarget.9977.
  69. Xu Y, Yue Q, Wei H, Pan G. PRAME induces apoptosis and inhibits proliferation of leukemic cells in vitro and in vivo. Int J Clin Exp Pathol. 2015;8(11):14549–55.
  70. Xu Y, Rong LJ, Meng SL, et al. PRAME promotes in vitro leukemia cells death by regulating S100A4/p53 signaling. Eur Rev Med Pharmacol Sci. 2016;20(6):1057–63.
  71. Bullinger L, Schlenk RF, Gotz M, et al. PRAME-Induced Inhibition of Retinoic Acid Receptor Signaling-Mediated Differentiation – Possible Target for ATRA Response in AML without t(15;17). Clin Cancer Res. 2013;19(9):2562–71. doi: 10.1158/1078-0432.CCR-11-2524.

Новые возможности лечения рецидивов и рефрактерной множественной миеломы (обзор литературы)

О.М. Вотякова

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Ольга Михайловна Вотякова, канд. мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: 8(499)324-92-09; e-mail: omvtk@yandex.ru

Для цитирования: Вотякова О.М. Новые возможности лечения рецидивов и рефрактерной множественной миеломы (обзор литературы). Клиническая онкогематология. 2017;10(4):425–34.

DOI: 10.21320/2500-2139-2017-10-4-425-434


РЕФЕРАТ

Несмотря на улучшение результатов лечения больных с впервые диагностированной множественной миеломой (ММ) благодаря внедрению в клиническую практику новых лекарственных препаратов и высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток, рецидивы неизбежно наступают у всех больных. Применение иммуномодулирующих препаратов (талидомида, леналидомида) и ингибитора протеасом бортезомиба позволило улучшить результаты лечения рецидивов ММ. Тем не менее развиваются повторные рецидивы и рефрактерность болезни к этим препаратам. Для этой категории больных необходимы новые лечебные стратегии, включая разработку более эффективных агентов среди существующих классов противомиеломных препаратов, исследование рациональной комбинации новых и традиционных лекарственных средств, а также поиск новых мишеней для препаратов, эффективных при ММ. В обзоре представлены основные клинические данные по эффективности и безопасности наиболее перспективных новых ингибиторов протеасом (карфилзомиба, иксазомиба), иммуномодулирующего препарата следующего поколения помалидомида, моноклональных антител (даратумумаба и элотузумаба).

Ключевые слова: ингибиторы протеасом, иммуномодулирующие препараты, моноклональные антитела, множественная миелома.

Получено: 14 марта 2017 г.

Принято в печать: 20 июня 2017 г.

Читать статью в PDF 

ЛИТЕРАТУРА

  1. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–5. doi: 10.1038/leu.2013.313.
  2. Ludwig H, Sonneveld P, Davies F, et al. European Perspective on Multiple Myeloma Treatment Strategies in 2014. Oncologist. 2014;19(8):829–44. doi: 10.1634/theoncologist.2014-0042.
  3. Rajkumar SV, Harousseau J-L, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691–5. doi: 10.1182/blood-2010-10-299487.
  4. Richardson PG, Sonnefeld P, Schuster M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood. 2007;110(11):3557–60. doi: 10.1182/blood-2006-08-036947.
  5. Dimopoulos MA, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357(21):2123–32. doi: 10.1056/NEJMoa070594.
  6. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357(21):2133–42. doi: 10.1056/NEJMoa070596.
  7. Weber D, Knight R, Chen C, et al. Prolonged overall survival with lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2007;110(11): Abstract 412.
  8. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867–74.
  9. Usmani S, Ahmadi T, Ng Y, et al. Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥ 3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD. Oncologist. 2016;21:1355–61. doi: 10.1634/theoncologist.2016-0104.
  10. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter International Myeloma Working Group study. Leukemia. 2012;26(1):149–57. doi: 10.1038/leu.2011.196.
  11. Bolli N, Avert-Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997. doi: 10.1038/ncomms3997.
  12. Lohr JG, Stojanov P, Carter SL, et al. Multiple Myeloma Research Consortium. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25(1):91–101. doi: 10.1016/j.ccr.2013.12.015.
  13. Egan JB, Shi CH, Tembe W, et al. Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012;120(5):1060–6. doi: 10.1182/blood-2012-01-405977.
  14. Yee AJ, Raje NS. Sequencing of nontransplant treatments in multiple myeloma patients with active disease. Hematology Am Soc Hematol Educ Program. 2016(1):495–503. doi: 10.1182/asheducation-2016.1.495.
  15. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142–52. doi: 10.1056/NEJMoa1411321.
  16. Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621–34. doi: 10.1056/NEJMoa1516282.
  17. Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373(7):621–31. doi: 10.1056/NEJMoa1505654.
  18. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375(14):1319–31. doi: 10.1056/NEJMoa1607751.
  19. Kuhn DJ, Orlowski RZ, Bjorklund CC. Second generation proteasome inhibitors: carfilzomib and immunoproteasome-specific inhibitors (IPSIs). Curr Cancer Drug Targets. 2011;11(3):285–95. doi: 10.2174/156800911794519725.
  20. Siegel DS, Martin T, Wang M, et al. A phase 2 study of single agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120(14):2817–25. doi: 10.1182/blood-2012-05-425934.
  21. Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2015;17(1):27–38. doi: 10.1016/S1470-2045(15)00464-7.
  22. Avet-Loiseau H, Fonseca R, Siegel D, et al. Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone Vs Lenalidomide and Dexamethasone in Patients with Relapsed Multiple Myeloma Based on Cytogenetic Risk Status: Subgroup Analysis from the Phase 3 Study Aspire (NCT01080391). Blood. 2015;126(23):731.
  23. Kupperman E, Lee EC, Cao Y, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970–80. doi: 10.1158/0008-5472.CAN-09-2766.
  24. Lee EC, Fitzgerald M, Bannerman B, et al. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res. 2011;17(23):7313–23. doi: 10.1158/1078-0432.CCR-11-0636.
  25. San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, Phase III trial. Lancet Oncol. 2013;14(11):1055–66. doi: 10.1016/S1470-2045(13)70380-2.
  26. Dimopoulos MA, Weisel KC, Song KW, et al. Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone. Haematologica. 2015;100(10):1327–33. doi: 10.3324/haematol.2014.117077.
  27. Dimopoulos MA, Leleu X, Palumbo A, et al. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia. 2014;28(8):1573–85. doi: 10.1038/leu.2014.60.
  28. ИМНОВИД® (IMNOVID®) инструкция по применению [электронный документ]. Доступно по: https://www.vidal.ru/drugs/imnovid__44356. Ссылка активна на 31.07.2017.[IMNOVID® instruction for medical use [Internet]. Available from: https://www.vidal.ru/drugs/imnovid__44356. (accessed 31.07.17) (In Russ)]
  29. Baz RC, Martin TG, Lin H-Y, et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016;127(21):2561–8. doi: 10.1182/blood-2015-11-682518.
  30. Lacy MQ, LaPlant BR, Laumann KM, et al. Pomalidomide, Bortezomib and Dexamethasone (PVD) for Patients with Relapsed Lenalidomide Refractory Multiple Myeloma (MM). Blood. 2014;124(21):304.
  31. Collins SM, Bakan CE, Swartzel GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013;62(12):1841–9. doi: 10.1007/s00262-013-1493-8.
  32. Veillette A, Guo H. CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma. Crit Rev Oncol Hematol. 2013;88(1):168–77. doi: 10.1016/j.critrevonc.2013.04.003.
  33. Lonial S, Richardson P, Mateos M-V, et al. ELOQUENT-2 update: Phase III study of elotuzumab plus lenalidomide/dexamethasone (ELd) vs Ld in relapsed/refractory multiple myeloma (RRMM)—Identifying responders by subset analysis. 2016 ASCO Annual Meeting. Poster 8037. Available from: http://meetinglibrary.asco.org/record/126339/abstract (accessed 31.07.17).
  34. Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121(4):482–8. doi: 10.1309/74r4-tb90-buwh-27jx.
  35. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J. Immunol. 2011;186(3):1840–8. doi: 10.4049/jimmunol.1003032.
  36. Lammerts van Bueren J, Jakobs D, Kaldenhoven N, et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79. Blood. 2014;124(21):3474.
  37. Overdijk MB, Verploegen S, Bogels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. mAbs. 2015;7(2):311–21. doi: 10.1080/19420862.2015.1007813.
  38. Jansen JHM, Boross P, Overdijk MB, et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking. Blood. 2012;120(21): Abstract 2974.
  39. Krejcik J, Casneuf T, Nijhof I, et al. Immunomodulatory effects and adaptive immune response to daratumumab in multiple myeloma. Blood. 2015:126(23): Abstract 3037.
  40. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207–19. doi: 10.1056/NEJMoa1506348.
  41. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551–60. doi: 10.1016/S0140-6736(15)01120-4.
  42. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128(1):37–44. doi: 10.1182/blood-2016-03-705210.
  43. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375:754–66. doi: 10.1056/NEJMoa1606038.

Нарушенный метаболизм метионина в злокачественных клетках — потенциальная мишень для противоопухолевой терапии

В.С. Покровский1, Д.Ж. Давыдов1, Н.В. Ануфриева2, Д.Д. Жданов3, Е.М. Трещалина1, Т.В. Демидкина2, Е.А. Морозова2

1 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, лаборатория комбинированной терапии опухолей, Каширское ш., д. 24, Москва, Российская Федерация, 154478

2 ФГБУН «Институт молекулярной биологии им. В.А. Энгельгардта» РАН, ул. Вавилова, д. 32, Москва, Российская Федерация, 119991

3 ФГБУ «НИИ биомедицинской химии им. В.Н. Ореховича», Погодинская ул., д. 10, стр. 8, Москва, Российская Федерация, 119121

Для переписки: Вадим Сергеевич Покровский, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 154478; тел.: 8(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

Для цитирования: Покровский В.С., Давыдов Д.Ж., Ануфриева Н.В. и др. Нарушенный метаболизм метионина в злокачественных клетках — потенциальная мишень для противоопухолевой терапии. Клиническая онкогематология. 2017;10(3):324–32.

DOI: 10.21320/2500-2139-2017-10-3-324-332


РЕФЕРАТ

В обзоре представлены особенности клеточного метаболизма метионина, а также известные данные о механизмах развития метиониновой зависимости в злокачественных клетках. Рассмотрены возможности использования безметиониновой диеты для контроля опухолевого роста у больных с различными формами рака. Сгруппированы и обобщены новейшие сведения о метионин-γ-лиазе — ферменте, обеспечивающем элиминацию метионина из плазмы. Раскрыта его роль в качестве потенциального противоопухолевого фермента. Обобщены сведения о продуцентах метионин-γ-лиазы, активности данного фермента, полученного из различных источников, и сведения о моделях опухолей и клеточных культурах, проявляющих метиониновую зависимость.

Ключевые слова: метионин-γ-лиаза, метионин, метиониновая зависимость, злокачественные клетки, рак, противоопухолевые ферменты, противоопухолевая терапия.

Получено: 16 декабря 2016 г.

Принято в печать: 6 марта 2017 г.

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ЛИТЕРАТУРА

  1. Thomas D, Surdin-Kerjan Y. Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1997;61(4):503–32.
  2. Ravanel S, Gaki B, Job D, Douce R. The specific features of methionine biosynthesis and metabolism in plants. Proc Natl Acad Sci USA. 1998;95(13):7805–12. doi: 10.1073/pnas.95.13.7805.
  3. Sekowska A, Kung H, Danchin A, et al. Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction. J Mol Microbiol Biotechnol. 2000;2(2):145–77.
  4. Guedes RL, Prosdocimi F, Fernandes GR, et al. Amino acids biosynthesis and nitrogen assimilation pathways: A great genomic deletion during eukaryotes. BMC Genom. 2011;12(Suppl 4):S2. doi: 10.1186/1471-2164-12-S4-S2.
  5. Satishchandran C, Taylor JC, Markham GD, et al. Novel Escherichia coli K-12 mutants impaired in S-adenosylmethionine synthesis. J Bacteriol. 1990;172(8):4489–96. doi: 10.1128/jb.172.8.4489-4496.1990.
  6. Zingg JM. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis. 1997;18(5):869–82. doi: 10.1093/carcin/18.5.869.
  7. Krasinskas A, Bartlett DL, Cieply K, et al. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol. 2010;23(4):531–8. doi: 10.1038/modpathol.2009.186.
  8. Roje S. S-Adenosyl-L-methionine: Beyond the universal methyl group donor. Phytochemistry 2006;67(15):1686-1698. doi: 10.1016/j.phytochem.2006.04.019.
  9. Anderson ME. Glutatione: an overview of biosynthesis and modulation. Chem Biol Interact. 1998;111(112):1–14. doi: 10.1016/s0009-2797(97)00146-4.
  10. Thomas T, Tomas TJ. Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci. 2001;58(2):244–58. doi: 10.1007/PL00000852.
  11. Pirkov I, Norbeck J, Gustafsson L, et al. A complete inventory of all enzymes in the eukaryotic methionine salvage pathway. FEBS J. 2008;275(16):4111–20. doi: 10.1111/j.1742-4658.2008.06552.x.
  12. Quash G, Roch AM, Chantepie J, et al. Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells. Biochem J. 1995;305(3):1017–25. doi: 10.1042/bj3051017.
  13. Bassila C, Ghemrawi R, Flayac J, et al. Methionine synthase and methionine synthase reductase interact with MMACHC and with MMADHC. Biochim Biophys Acta. 2017;1863(1):103–12. doi: 10.1016/j.bbadis.2016.10.016.
  14. Морозова Е.А., Куликова В.В., Яшин Д.В. и др. Кинетические характеристики и цитотоксическая активность рекомбинантных препаратов метионин–гамма-лиазы Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis и Citrobacter freundii. Acta Naturae. 2013;5:54–60. [Morozova EA, Kulikova VV, Yashin DV, et al. Kinetic parameters and cytotoxic activity of recombinant methionine γ-lyase from Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis and Citrobacter freundii. Acta Naturae. 2013;5:54–60. (In Russ)]
  15. Cavuoto P, Fenech MF. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 2012;38(6):726–36. doi: 10.1016/j.ctrv.2012.01.004.
  16. Sugimura T, Birnbaum SM, Winitz M, et al. Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid. Arch Biochem Bioophys. 1959;81(2):448–55. doi: 10.1016/0003-9861(59)90225-5.
  17. Buch L, Streeter D, Halpern RM, et al. Inhibition of transfer ribonucleic acid methylase activity from several human tumors by nicotinamide and nicotinamide analogs. Biochemistry. 1972;11(3):393–7. doi: 10.1021/bi00753a015.
  18. Halpern BC, Clark BR, Hardy DN, et al. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc Natl Acad Sci USA. 1974;71(4):1133–6. doi: 10.1073/pnas.71.4.1133.
  19. Judde JG, Ellis M, Frost P, et al. Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells. Cancer Res. 1989;49(17):4859–65.
  20. Hoffman RM, Jacobsen J. Reversible growth arrest in simian virus 40-transformed human fibroblasts. Proc Natl Acad Sci USA. 1980;77(12):7306–10. doi: 10.1073/pnas.77.12.7306.
  21. Guo H, Lishko VK, Herrera H, et al. Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Cancer Res. 1993;53(23):5676–9.
  22. Breillout F, Antoine E, Poupon MF. Methionine dependency of malignant tumors: a possible approach for therapy. J Natl Cancer Inst. 1990;82(20):1628–32. doi: 10.1093/jnci/82.20.1628.
  23. Lu S, Epner DE. Molecular mechanisms of cell cycle block by methionine restriction in human prostate cancer cells. Nutr Cancer. 2000;38(1):123–30. doi: 10.1207/S15327914NC381_17.
  24. Poirson-Bichat F, Goncalves RA, Miccoli L, et al. Methionine depletion enhances the antitumoral efficacy of cytotoxic agents in drug-resistant human tumor xenografts. Cancer Res. 2000;6(2):643–53.
  25. Guo H, Herrera H, Groce A, et al. Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res. 1993;53(11):2479–83.
  26. Kim DH, Muto M, Kuwahara Y, et al. Array-based comparative genomic hybridization of circulating esophageal tumor cells. Oncol Rep. 2006;16(5):1053–9. doi: 10.3892/or.16.5.1053.
  27. Poirson-Bichat F, Gonfalone G, Bras-Gone RA, et al. Growth of methionine dependent human prostate cancer (PC-3) is inhibited by ethionine combined with methionine starvation. Br J Cancer. 1997;75(11):1605–12. doi: 10.1038/bjc.1997.274.
  28. Jo YK, Park MH, Choi H, et al. Enhancement of the Antitumor Effect of Methotrexate on Colorectal Cancer Cells via Lactate Calcium Salt Targeting Methionine Metabolism / Nutr Cancer. 2017;69(4):663–73. doi: 10.1080/01635581.2017.1299879.
  29. Kreis W, Goodenow M. Methionine requirement and replacement by homocysteine in tissue cultures of selected rodent and human malignant and normal cells. Cancer Res. 1978;38(8):2259–62.
  30. Kennelly JC, Blair JA, Pheasant AE. Metabolism of 5-methyltetrahydrofolate by rats bearing the Walker 256 carcinosarcoma. Br J Cancer. 1982;46(3):440–3. doi: 10.1038/bjc.1982.222.
  31. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Investig Med. 1998;21(3):151–8.
  32. Bergstrom M, Ericson K, Hagenfeldt L, et al. PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. J Comput Assist Tomogr. 1987;11(2):208–13. doi: 10.1097/00004728-198703000-00002.
  33. Stern PH, Hoffman RM. Elevated overall rates of transmethylation in cell lines from diverse human tumors. In Vitro. 1984;20(8):663–73. doi: 10.1007/bf02619617.
  34. Hoffman RM. Altered methionine metabolism and transmethylation in cancer. Anticancer Res. 1985;5(1):1–30.
  35. Давыдов Д.Ж., Морозова Е.А., Ануфриева Н.В. и др. Динамика содержания метионина в плазме крови мышей после введения метионин-гамма-лиазы. Российский биотерапевтический журнал. 2017;16(Suppl 1):28–9. [Davydov DZh, Morozova EA, Anufrieva NV, et al. The changes in plasma methionin concentrations in mice after methionine-gamma-lyase injection. Rossiiskii bioterapevticheskii zhurnal. 2017;16(Suppl 1):28–9. (In Russ)]
  36. Hoffman RM. Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis: a review and synthesis. Biochim Biophys Acta. 1983;738(1–2):49–87. doi: 10.1016/0304-419x(84)90019-2.
  37. de Oliveira SF, Ganzinelli M, Chila R, et al. Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines. PLoS One. 2016;11(1):e0145647. doi: 10.1371/journal.pone.0145647.
  38. Nobori T, Karras JG, Della Ragione F, et al. Absence of methilthioadenosine phosphorylase in human gliomas. Cancer Res. 1991;51(12):3193–7.
  39. Schmid M, Malicki D, Nobori T, et al. Homozygous deletions of methilthioadenosine phosphorylase (MTAP) are more frequent then p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancer (NSCLC). Oncogene. 1998;17(20):2669–75. doi: 10.1038/sj.onc.1202205.
  40. M’soka TJ, Nishioka J, Taga A, et al. Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay. Leukemia. 2000;14(5):935–40. doi: 10.1038/sj.leu.2401771.
  41. Garcia-Castellano JM, Villanueva A, Healey JH, et al. Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clin Cancer Res. 2002;8(3):782–7.
  42. Behrmann I, Wallner S, Komyod W, et al. Characterization of methylthioadenosin phosphorylase (MTAP) expression in malignant melanoma. Am J Pathol. 2003;162(2):683–90. doi: 10.1016/S0002-9440(10)63695-4.
  43. Komatsu A, Nagasaki K, Fujimori M, et al. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol. 2008;33(2):261–70.
  44. Nobori T, Miura K, Wu DJ, et al. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994;368(6473):753–6. doi: 10.1038/368753a0.
  45. Nobori T, Takabayashi K, Tran P, et al. Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers. Proc Natl Acad Sci USA. 2000;93(12):6203–8. doi: 10.1073/pnas.93.12.6203.
  46. Brat DJ, James CD, Jedlicka AE, et al. Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol. 1999;154(5):1431–8. doi: 10.1016/S0002-9440(10)65397-7.
  47. Christopher SA, Diegelman P, Porter CW, et al. Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. Cancer Res. 2002;62(22):6639–44.
  48. Jagasia AA, Block JA, Diaz MO, et al. Partial deletions of the CDKN2A and MTS2 putative tumor suppressor genes in a myxoid chondrosarcoma. Cancer Lett. 1996:105(1):77–90. doi: 10.1016/0304-3835(96)04273-5.
  49. Jagasia AA, Block JA, Qureshi A, et al. Chromosome 9 related aberration and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosarcomas. Cancer Lett. 1996;105(1):91–103. doi: 10.1016/0304-3835(96)04274-7.
  50. Powel EL, Leoni LM, Canto MI, et al. Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Phatol. 2005;29(11):1497–504. doi: 10.1097/01.pas.0000170349.47680.e8.
  51. Kim J, Kim MA, Min SY, et al. Downregulation of methylthioadenosin phosphorylase by homozygous deletion in gastric carcinoma. Genes Chromos Cancer. 2011;50(6):421–33. doi: 10.1002/gcc.20867.
  52. Huang H-Y, Li S-H, Yu S-C, et al. Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors. Clin Cancer Res. 2009;15(22):6963–72. doi: 10.1158/1078-0432.CCR-09-1511.
  53. Suzuki T, Maruno M, Wada K, et al. Genetic analysis of human glioblastomas using a genomic microarray system. Brain Tumor Pathol. 2004;21(1):27–34. doi: 10.1007/bf02482174.
  54. Zhang H, Chen ZH, Savarese TM, et al. Codeletion of the genes for p16INK4 methihthioadenosine phosphorylase, interferon-alpha1, interferon-beta1, and other 9p21 markers in human malignant cell lines. Cancer Genet Cytogenet. 1996;86(1):22–8. doi: 10.1016/0165-4608(95)00157-3.
  55. Perry A, Nobory T, Ru N, et al. Detection of p16 gene deletions in gliomas: comparison of fluorescence in situ hybridization (FISH) versus quantitative PCR. J Neuropathol Exp Neurol. 1997;56(9):999–1008. doi: 10.1097/00005072-199709000-00005.
  56. Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span . J Nutr. 1993;123(2):269–74.
  57. Efferth DE, Miyachi H, Drexler HG, Gebhart E. Methionine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells. Blood Cells Mol Dis. 2002;28(1):47–56. doi: 10.1006/bcmd.2002.0483.
  58. Bertin R, Acquaviva C, Mirebeau D, et al. CDKN2A, CDKN2B and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9p21 deletions in childhood acute lymphoblastic leukemia. Genes Chromos Cancer. 2003;37(1):44–57. doi: 10.1002/gcc.10188.
  59. Usvasalo A, Ninomiya S, Raty R, et al. Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analyses. Genes Chromos Cancer. 2010;49(4):309–18. doi: 10.1002/gcc.20741.
  60. Kamath A, Tara H, Xiang B, et al. Double-minute MYC amplification and deletion of MTAP, CDKN2A, CDKN2B and ELAVL2 in an acute myeloid leukemia characterized by oligonucleotide-array comparative genomic hybridization. J Cancer Genet Cytogenet. 2008;183(2):117–20. doi: 10.1016/j.cancergencyto.2008.02.011.
  61. Marce S, Balague O, Colomo L, et al. Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy. Clin Cancer Res. 2006;12(12):3754–61. doi: 10.1158/1078-0432.CCR-05-2780.
  62. Dreyling MH, Roulston D, Bohlander SK, et al. Codelition of CDKN2 and MTAP genes in a subset of non-Hodgkin’s lymphoma may be associated with histologic transformation from low-grade to diffuse large-cell lymphoma. Genes Chromos Cancer. 1998;22(1):72–8. doi: 10.1002/(sici)1098-2264(199805)22:1<72::aid-gcc10>3.3.co;2-g.
  63. Illei PB, Busch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Cancer Res. 2003;9(6):2108–13.
  64. Mora J, Alaminos M, de Torres C, et al. Comprehensive analysis of the 9p21 region in neuroblastoma suggests a role for genes mapping to 9p21–23 in the biology of favorable stage 4 tumours. Br J Cancer. 2004;91(6):1112–8. doi: 10.1038/sj.bjc.6602094.
  65. Hustinx SR, Hruban RH, Leoni LM, et al. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy. Cancer Biol Ther. 2005;4(1):83–6. doi: 10.4161/cbt.4.1.1380.
  66. Hustinx SR, Leoni ML, Yeo CJ, et al. Concordant loss of MTAP and p16/CDRN2A expressions in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol. 2005;18(7):959–63. doi: 10.1038/modpathol.3800377.
  67. Chen ZH, Zhang H, Savarese TM. Gene deletion chemoselectivity: codeletion of the genes for p16 (INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for. Cancer Res. 1996;56(5):1083–90.
  68. Brownhill SC, Taylor C, Burchill SA. Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT. Br J Cancer. 2007;96(12):1914–23. doi: 10.1038/sj.bjc.6603819.
  69. Conway C, Beswick S, Elliott F. Deletion at chromosome arm 9p in relation to BRAF and NRAS mutation and prognostic significance for primary melanoma. Genes Chromos Cancer. 2010;49(5):425–38. doi: 10.1002/gcc.20753.
  70. Worsham MJ, Chem KM, Tiwari N, et al. Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a) and MTAP genes in head and neck squamous cell carcinoma. Arch Otol Head Neck Surg. 2006;132(4):409–15. doi: 10.1001/archotol.132.4.409.
  71. Mirebeau D, Acquaviva C, Suciu S, et al. The prognostic significance of CDKN2A, CDKN2B and EORTC studies 58881 and 58951. Haematologica. 2006;91(7):881–5.
  72. Tang B, Li YN, Kruger WD. Defects in methylthioadenosine phosphorylase is associated with but not responsible for methionine-dependent tumor cell growth. Cancer Res. 2000;60(19):5.
  73. Basu I, Locker J, Cassera MB, et al. Growth and metastases of human lung cancer are inhibited in mouse xenografts by a transition state analogue of 5ʹ-methilthioadenosine. J Biol Chem. 2010;286(6):4902–11. doi: 10.1074/jbc.M110.198374.
  74. Subhi AL, Diegelman P, Porter CW, et al. Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites. J Biol Chem. 2003;278(50):49868–73. doi: 10.1074/jbc.M308451200.
  75. Kenyon SH, Waterfield CJ, Timbrell JA, et al. Methionine synthase activity and sulphur amino acid levels in the rat liver tumor cells HTS and Phi-1. J. Biochem Pharmacol. 2002;63(3):381–91. doi: 10.1016/s0006-2952(01)00874-7.
  76. Ma E, Iwasaki M, Junko I, et al. Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women. BMC Cancer. 2009;24(9):122. doi: 10.1186/1471-2407-9-122.
  77. Stern PH, Wallace CD, Hoffman RM. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J Cell physiol. 1984;119(1):29–34. doi: 10.1002/jcp.1041190106.
  78. Lu M, Wang F, Qiu J. Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects. Breast Cancer Res Treat. 2010;123(1):213–7. doi: 10.1007/s10549-010-0755-9.
  79. Linnebank M, Fliessbach K, Kolsch H, et al. The methionine synthase polymorphism c.2756Aright curved arrow G (D919G) is relevant for disease-free longevity. Int J Mol Med. 2005;16(4):759–61.
  80. Dhillon V, Thomas P, Fenech M. Effect of common polymorphisms in folate uptake and metabolism genes on frequency of micronucleated lymphocytes in a South Australian cohort. Mutat Res. 2009;665(1–2):1–6. doi: 10.1016/j.mrfmmm.2009.02.007.
  81. Beetstra S, Suthers G, Dhillon V, et al. Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 mutation carriers with and without breast cancer. Cancer Epidemiol Biomark Prev. 2008;17(10):2565–71. doi: 10.1158/1055-9965.EPI-08-0140.
  82. Drennan CL, Huang S, Drummond J, et al. How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase. Science. 1994;266(5191):1669–74. doi: 10.1126/science.7992050.
  83. Tisdale MJ. Methionine metabolism in Walker carcinosarcoma in vitro. Eur J Cancer. 1980;16(3):407–14. doi: 10.1016/0014-2964(80)90360-6.
  84. Liteplo RG, Hipwell SE, Rosenblatt DS, et al. Changes in cobalamin metabolism are associated with the altered methionine auxotrophy of highly growth autonomous human melanoma. J Cell Physiol. 1991;149(2):332–8. doi: 10.1002/jcp.1041490222.
  85. Fiskerstrand T, Christensen B, Tysnes OB, et al. Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. Cancer Res. 1994;54(18):4899–906.
  86. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Invest Med. 1998;21(3):151–8.
  87. Tang B, Mustafa A, Gupta S, et al. Methionine-deficient diet induces post-transcriptional down-regulation of cystathionine beta-synthase. Nutrition. 2009;26(11–12):170–5. doi: 10.1016/j.nut.2009.10.006.
  88. Breillout F, Hadida F, Echinard-Garin P, et al. Decreased rat rhabdomyosarcoma pulmonary metastases in response to low methionine diet. Anticancer Res. 1987;7(4b):861–7.
  89. Komninou D, Leutzinger Y, Reddy BS, et al. Methionine restriction inhibits colon carcinogenesis. Nutr Cancer. 2006;54(2):202–8. doi: 10.1207/s15327914nc5402_6.
  90. Graziosi L, Mencarelli A, Renga B, et al. Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination. J Gastrointest Surg. 2013;17(1):39–49. doi: 10.1007/s11605-012-1996-1.
  91. Theuer RC. Effect of essential amino acid restriction on the growth of female C57BL mice and their implanted BW10232 adenocarcinomas. J Nutr. 1971;101(2):223–32.
  92. Caro P, Gomez J, Sanchez I, et al. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuven Res. 2009;12(6):421–34. doi: 10.1089/rej.2009.0902.
  93. Ryu CS, Kwak HC, Lee KS, et al. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells. Toxicol Appl Pharmacol. 2011;15;255(1):94–102. doi: 10.1016/j.taap.2011.06.004.
  94. Goseki N, Endo M. Thiol depletion and chemosensitization on nimustine hydrochloride by methionine-depleting total parenteral nutrition. Tohoku J Exp Med. 1990;161(3):227–39. doi: 10.1620/tjem.161.227.
  95. Hoshiya Y, Guo H, Kubota T, et al. Human tumors are methionine dependent in vivo. Anticancer Res. 1995;15(3):717–8.
  96. Epne DE, Morrow S, Wilcox M, Houghton JL. Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase l clinical trial of dietary methionine restriction. Nutr Cancer. 2002;42(2):158–66. doi: 10.1207/S15327914NC422_2.
  97. Goseki N, Yamazaki S, Shimojyu K, et al. Synergistic effect of methionine-depleting total parenteral nutrition with 5-fluorouracil on human gastric cancer: a randomized, prospective clinical trial. Jpn J Cancer Res. 1995;86(5):484–9. doi: 10.1111/j.1349-7006.1995.tb03082.x.
  98. Durando X, Farges MC, Buc E, et al. Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: a feasibility study. Oncology. 2008;78(3–4):205–9. doi: 10.1159/000313700.
  99. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065–70. doi: 10.1097/01.ju.0000169487.49018.73.
  100. McCarty M, Barroso-Aranda J, Contreras F, et al. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009;72(2):125–8. doi: 10.1016/j.mehy.2008.07.044.
  101. Kack H, Sandmark J, Gibson K, et al. Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5ʹ-phosphate-dependent enzymes. J Mol Biol. 1999;291:857–76. doi: 10.1006/jmbi.1999.2997.
  102. Fernandes HS, Silva Teixeira CS, Fernandes PA, et al. Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections. Expert Opin Ther Pat. 2017;27(3):283–97. doi: 10.1080/13543776.2017.1254194.
  103. Gay F, Aguera K, Senechal K, et al. Methionine tumor starvation by erythrocyte-encapsulated methionine gamma-lyase activity controlled with per os vitamin B6. Cancer Med. 2017. doi: 10.1002/cam4.1086.
  104. Покровский В.С., Трещалина Е.М. Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения. Клиническая онкогематология. 2014;7(1):28–38. [Pokrovskiy VS, Treshchalina YeM. Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use. Klinicheskaya onkogematologiya. 2014;7(1):28–38. (In Russ)]
  105. Манухов И.В., Мамаева Д.В., Морозова Е.А. и др. L-метионин–гамма-лиаза Citrobacter freundii: клонирование гена и кинетические параметры фермента. Биохимия. 2006;71(4):454–63. [Manukhov IV, Mamaeva DV, Morozova EA, et al. L-methionine γ-lyase from Citrobacter freundii: cloning of the gene and kinetic parameters of the enzyme. Biokhimiya. 2006;71(4):454–63. (In Russ)]
  106. Cellarier E, Durando X, Vasson MP, et al. Methionine dependency and cancer treatment. Cancer Treat Rev. 2003;29(6):489–99. doi: 10.1016/s0305-7372(03)00118-x.
  107. Tan Y, Xu M, Hoffman RM. Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells in vitro. Anticancer Res. 2010;30:1041–6.
  108. Kreis W, Hession C. Isolation and purification of L-methionine-alpha-deamino-gamma-mercaptomethane-lyase (L-methioninase) from Clostridium sporogenes. Cancer Res. 1973;33:1862–5.
  109. Hori H, Takabayashi K, Orvis L, et al. Gene cloning and characterization of Pseudomonas putida L-methionine-alpha-deamino-gamma-mercaptomethane-lyase. Cancer Res. 1996;56(9):2116–22.
  110. El-Sayed SA, Shouman HM, Nassrat HM. Pharmacokinetics, immunogenicity and anticancer efficiency of Aspergillus flavipes L-methioninase. Enzyme Microb Technol. 2012;51(4):200–10. doi: 10.1016/j.enzmictec.2012.06.004.
  111. Huang K-Y, Hu H-Y, Tang Y-L, et al. High-level expression, purification and large-scale production of L-methionine γ-Lyase from Ideomarina as a novel anti-leucemic drug. Mar Drugs. 2015;13(8):5492–507. doi: 10.3390/md13085492.
  112. Yano S, Li S, Han Q, et al. Selective methioninase-inducted trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity. Oncotarget. 2014;5(18):8729–36. doi: 10.18632/oncotarget.2369.
  113. Nagahama T, Goseki N, Endo M. Doxorubicin and vincristine with methionine depletion contributed to survival in the Yoshida sarcoma bearing rats. Anticancer Res. 1998;18(1):25–31.
  114. Machrover D, Zittoun J, Broet Ph, et al. Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid. Biochem Pharmacol. 2001;61(7):867–76. doi: 10.1016/s0006-2952(01)00560-3.
  115. Smiraglia DJ. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum Mol Genet. 2001;10(13):1413–9. doi: 10.1093/hmg/10.13.1413.
  116. Jeanblanc M, Mousli M, Hopfner R, et al. The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle. Oncogene. 2005;24(49):7337–45. doi: 10.1038/sj.onc.1208878.
  117. Hu J, Cheung NK. Methionine depletion with recombinant methioninase: In vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drug. Int J Cancer. 2009;124(7):1700–6. doi: 10.1002/ijc.24104.
  118. Kokkinakis DM, Schold H, Hori H, et al. Effect of long-term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice. Nutr Cancer. 1997;29(3):195–204. doi: 10.1080/01635589709514624.
  119. Tan Y, Xu M, Guo H, et al. Anticancer efficacy of methioninase in vivo. Anticancer Res. 1996;16(6С):3931–6.
  120. Tan Y, Sun X, Xu M, et al. Efficacy of recombinant methioninase in combination with cisplatin on human colon tumors in nude mice. Clin Cancer Res. 1999;5(8):2157–63.
  121. Yoshioka T, Wada T, Uchida N, et al. Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase. Cancer Res. 1998;58(12):2583–7.
  122. Hoshiya Y, Kubota T, Matsuzaki SW, et al. Methionine starvation modulates the efficacy of cisplatin on human breast cancer in nude mice. Anticancer Res. 1996;16(6B):3515–7.
  123. Kokkinakis DM, Hoffman RM, Frenkel EP, et al. Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice. Cancer Res. 2001;61(10):4017–23.
  124. Tan Y, Zavala JSr, Xu M, et al. Serum methionine depletion without side effects by methioninase in metastatic breast cancer patients. Anticancer Res. 1996;16(6):3937–42.
  125. Morozova EA, Anufrieva NV, Davydov DZ, et al. Plasma methionine depletion and pharmacokinetic properties in mice of methionine γ-lyase from Citrobacter freundii, Clostridium tetani and Clostridium sporogenes. Biomed Pharmacother. 2017;88:978–84. doi: 10.1016/j.biopha.2017.01.127.
  126. Покровский В.С., Лесная Н.А., Трещалина Е.М. и др. Перспективы разработки новых ферментных противоопухолевых препаратов. Вопросы онкологии. 2011;57(2):155–64. [Pokrovskii VS, Lesnaya NA, Treshchalina EM, et al. Perspectives in the development of new enzyme anticancer treatments. Voprosy onkologii. 2011;57(2):155–64. (In Russ)]
  127. Покровская М.В., Покровский В.С., Соколов Н.Н. Дифференциальная среда для выявления штаммов бактерий-продуцентов L-аспарагиназ. Прикладная биохимия и микробиология. 2011;47(2):183–6. [Pokrovskaya MV, Pokrovskii VS, Sokolov NN, et al. Differential medium for revealing bacterial producer strains of L-asparaginases.) Prikladnaya biokhimiya i mikrobiologiya. 2011;47(2):183–6. (In Russ)]
  128. Pokrovskii VS, Pokrovskaya MV, Aleksandrova SS, et al. Physicochemical properties and antiproliferative activity of recombinant Yersinia pseudotuberculosis L-asparaginase. Appl Biochem Microbiol. 2013;49(1):18–22. doi: 10.1134/s000368381301016x.
  129. Pokrovskaya MV, Pokrovskiy VS, Aleksandrova SS, et al. Recombinant intracellular Rhodospirillum rubrum L-asparaginase with low L-glutaminase activity and antiproliferative effect. Biochem (Moscow) Suppl. Series B: Biomed Chem. 2012;6(2):123–31. doi: 10.1134/s1990750812020096.
  130. Sidoruk KV, Bogush VG, Pokrovsky VS, et al. Creation of a producent, optimization of expression, and purification of recombinant Yersinia pseudotuberculosis L-asparaginase. Bull Exp Biol Med. 2011;152(2):219–23. doi: 10.1007/s10517-011-1493-7.
  131. Pokrovsky VS, Pokrovskaya MV, Aleksandrova SS, et al. Comparative immunogenicity and structural analysis of epitopes of different bacterial L-asparaginases. BMC Cancer. 2016;16(1):89. doi: 10.1186/s12885-016-2125-4.
  132. Sannikova EP, Bulushova NV, Cheperegin SE, et al. The modified heparin-binding L-asparaginase of Wolinella succinogenes. Mol Biotechnol. 2016;58(8–9):528–39. doi: 10.1007/s12033-016-9950-1.
  133. Pokrovskaya MV, Aleksandrova SS, Pokrovsky VS, et al. Identification of functional regions in the Rhodospirillum rubrum L-asparaginase by site-directed mutagenesis. Mol Biotechnol. 2015;57(3):251–64. doi: 10.1007/s12033-014-9819-0.
  134. Покровский В.С., Лукашева Е.В., Трещалина Е.М. и др. Экспериментальная оценка синергизма цисплатина с L-лизин-α-оксидазой. Вопросы онкологии. 2014;60(1):90–3. [Pokrovskii VS, Lukasheva EV, Treshchalina EM, et al. Experimental evaluation of synergism of cisplatin with L-lysine-α-oxidase.) Voprosy onkologii. 2014;60(1):90–3. (In Russ)]
  135. Покровский В.С., Трещалина Е.М., Трещалин И.Д. и др. Оценка противоопухолевой эффективности комбинации L-лизин-α-оксидазы и иринотекана в эксперименте. Онкология. 2012;2:58–61. [Pokrovskii VS, Treshchalina EM, Treshchalin ID, et al. Evaluation of the antitumor efficacy of a combination of L-lysine α-oxidase and irinotecan in the experiment. Onkologiya. 2012;2:58–61. (In Russ)]

Цитогенетические и молекулярно-генетические факторы прогноза острых лимфобластных лейкозов

А.В. Мисюрин

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Андрей Витальевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; e-mail: and@genetechnology.ru

Для цитирования: Мисюрин А.В. Цитогенетические и молекулярно-генетические факторы прогноза острых лимфобластных лейкозов. Клиническая онкогематология. 2017;10(3):317–23.

DOI: 10.21320/2500-2139-2017-10-3-317-23


РЕФЕРАТ

В обзоре представлены характерные и воспроизводимые при острых лимфобластных лейкозах (ОЛЛ) перестройки хромосом, которые можно обнаружить при стандартном цитогенетическом исследовании (окраска на G-полосы) или методом FISH. Более тонкие генетические изменения, недоступные для наблюдения цитогенетиков, выявляются с помощью современных методов молекулярно-биологической диагностики. Показано прогностическое значение цитогенетических и молекулярно-генетических маркеров ОЛЛ. Представлен минимальный набор клинически значимых молекулярных маркеров, которые целесообразно исследовать при ОЛЛ.

Ключевые слова: острый лимфобластный лейкоз, хромосомная аномалия, химерный онкоген, экспрессия гена, мутация гена.

Получено: 3 декабря 2016 г.

Принято в печать: 8 марта 2017 г.

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ЛИТЕРАТУРА

  1. Гематология: национальное руководство. Под ред. О.А. Рукавицына. М.: ГЭОТАР-Медиа, 2015. 776 с. [Rukavitsyn OA, ed. Gematologiya: natsional’noe rukovodstvo. (Hematology: national guidelines.) Moscow: GEOTAR-Media Publ.; 2015. 776 p. (In Russ)]
  2. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013;381(9881):1943–55. doi: 10.1016/S0140-6736(12)62187-4.
  3. Shago M. Recurrent Cytogenetic Abnormalities in Acute Lymphoblastic Leukemia. Meth Mol Biol. 2017;1541:257–78. doi: 10.1007/978-1-4939-6703-2_21.
  4. Deshpande PA, Srivastava VM, Mani S, et al. Atypical BCR-ABL11 fusion transcripts in adult B-acute lymphoblastic leukemia, including a novel fusion transcript-e8a1. Leuk Lymphoma. 2016;57(10):2481–4. doi: 10.3109/10428194.2016.1151512.
  5. McGregor S, McNeer J, Gurbuxani S. Beyond the 2008 World Health Organization classification: the role of the hematopathology laboratory in the diagnosis and management of acute lymphoblastic leukemia. Semin Diagn Pathol. 2012;29(1):2–11.
  6. Zerbini MCN, Soares FA, Velloso EDRP, et al. World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 2008: major changes from the 3rd edition. Revista da Associacao Medica Brasileira. 2011;57(1):6–73. doi: 10.1590/S0104-42302011000100019.
  7. Paulsson K, Johansson B. High hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromos Cancer. 2009;48(8):637–60. doi: 10.1002/gcc.20671.
  8. Mrоzek K, Harper DP, Aplan PD. Cytogenetics and Molecular Genetics of Acute Lymphoblastic Leukemia. Hematol Oncol Clin North Am. 2009;23(5):1–20. doi: 10.1016/j.hoc.2009.07.001.
  9. Faderl S, Estrov Z. Residual disease in acute lymphoblastic leukemia of childhood: methods of detection and clinical relevance. Cyt Cell Mol Ther. 1998;4(2):73–85.
  10. Heerema NA, Raimondi SC, Anderson JR, et al. Specific extra chromosomes occur in a modal number dependent pattern in pediatric acute lymphoblastic leukemia. Genes Chromos Cancer. 2007;46(7):684–93. doi: 10.1002/gcc.20451.
  11. Woo JS, Alberti MO, Tirado CA. Childhood B-acute lymphoblastic leukemia: a genetic update. Exper Hematol Oncol. 2014;3(1):16. doi: 10.1186/2162-3619-3-16.
  12. Sutcliffe MJ, Shuster JJ, Sather HN, et al. High concordance from independent studies by the Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorABL1e prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children’s Oncology Group (COG) initiative. Leukemia. 2005;19(5):734–40. doi: 10.1038/sj.leu.2403673.
  13. Moorman AV, Richards SM, Martineau M, et al. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Blood. 2003;102(8):2756–62. doi: 10.1182/blood-2003-04-1128.
  14. Forestier E, Johansson B, Gustafsson G, et al. Prognostic impact of karyotypic findings in childhood acute lymphoblastic leukaemia: a Nordic series comparing two treatment periods. Br J Haematol. 2000;110(1):147–53.
  15. Raimondi SC, Pui CH, Hancock ML, et al. Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia. Leukemia. 1996;10(2):213–24.
  16. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008;111(5):2563–72. doi: 10.1182/blood-2007-10-116186.
  17. Oostlander AE, Meijer GA, Ylstra B. Microarray-based comparative genomic hybridization and its applications in human genetics. Clin Genet. 2004;66(6):488–95. doi: 10.1111/j.1399-0004.2004.00322.x.
  18. Rubnitz JE, Wichlan D, Devidas M, et al. Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children’s Oncology Group study. J Clin Oncol. 2008;26(13):2186–91. doi: 10.1200/JCO.2007.14.3552.
  19. Attarbaschi A, Mann G, Konig M, et al. Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis. Leukemia. 2004;18(10):1611–6. doi: 10.1038/sj.leu.2403471.
  20. Pullarkat V, Slovak ML, Kopecky KJ, et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood. 2008;111(5):2563–72. doi: 10.1182/blood-2007-10-116186.
  21. Stock W. Advances in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2008;6(7):487–8.
  22. Fielding AK, Rowe JM, Richards SM, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the international ALL trial MRC KALLXII/ECOG2993. Blood. 2009;113(19):4489–96. doi: 10.1182/blood-2009-01-199380.
  23. Yanada M, Matsuo K, Suzuki T, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a metaanalysis. Leukemia. 2005;19(8):1345–9. doi: 10.1038/sj.leu.2403838.
  24. Moorman AV, Richards SM, Robinson HM, et al. Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). Blood. 2007;109(6):2327–30. doi: 10.1182/blood-2006-08-040436.
  25. Heerema NA, Harbott J, Galimberti S, et al. Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia. 2004;18(4):693–702. doi: 10.1038/sj.leu.2403324.
  26. Wetzler M, Talpaz M, Estrov Z, Kurzrock R. CML: mechanisms of disease initiation and progression. Leuk Lymphoma. 1993;11(Suppl 1):47–50. doi: 10.3109/10428199309047863.
  27. Chessells JM, Swansbury GJ, Reeves B, et al. Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Br J Haematol. 1997;99(1):93–100.
  28. Chessells JM, Harrison CJ, Kempski H, et al. Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party. Leukemia. 2002;16(5):776–84. doi: 10.1038/sj.leu.2402468.
  29. Moorman AV, Raimondi SC, Pui CH, et al. No prognostic effect of additional chromosomal abnormalities in children with acute lymphoblastic leukemia and 11q23 abnormalities. Leukemia. 2005;19(4):557–63. doi: 10.1038/sj.leu.2403695.
  30. Pui CH, Sandlund JT, Pei D, et al. Results of therapy for acute lymphoblastic leukemia in black and white children. JAMA. 2003;290(15):2001–7. doi: 10.1001/jama.290.15.2001.
  31. Pui C-H, Chessells JM, Camitta B, et al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia. 2003;17(4):700–6. doi: 10.1038/sj.leu.2402883.
  32. Jeha S, Pei D, Raimondi SC, et al. Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1. Leukemia. 2009;23(8):1406–9. doi: 10.1038/leu.2009.42.
  33. Mrozek K. Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype. Semin Oncol. 2008;35:365–77. doi: 10.1053/j.seminoncol.2008.04.007.
  34. Wetzler M, Dodge RK, Mrozek K, et al. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood. 1999;93(11):3983–93.
  35. Bernard OA, Busson-LeConiat M, Ballerini P, et al. A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia. Leukemia. 2001;15(10):1495–504. doi: 10.1038/sj.leu.2402249.
  36. Graux C, Stevens-Kroef M, Lafage M, et al. Heterogeneous patterns of amplification of the NUP214-ABL11 fusion gene in T-cell acute lymphoblastic leukemia. Leukemia. 2009;23(1):125–33. doi: 10.1038/leu.2008.278.
  37. Quintas-Cardama A, Tong W, Manshouri T, et al. Activity of tyrosine kinase inhibitors against human NUP214-ABL11-positive T cell malignancies. Leukemia. 2008;22(6):1117–24. doi: 10.1038/leu.2008.80.
  38. Krawczyk J, Haslam K, Lynam P, et al. No prognostic impact of P2RY8-CRLF2 fusion in intermediate cytogenetic risk childhood B-cell acute lymphoblastic leukaemia. Br J Haematol. 2013;160(4):555–6. doi: 10.1111/bjh.12130.
  39. Hoelzer D. Personalized medicine in adult acute lymphoblastic leukemia. Haematologica. 2015;100(7):855–8. doi: 10.3324/haematol.2015.127837.
  40. Tsuzuki S, Taguchi O, Seto M. Promotion and maintenance of leukemia by ERG. Blood. 2011;117(14):3858–68. doi: 10.1182/blood-2010-11-320515.
  41. Mullighan CG, Su X, Zhang J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470–80. doi: 10.1056/NEJMoa0808253.
  42. Mullighan CG, Miller CB, Radtke I, et al. BCR-ABL11 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature. 2008;453(7191):110–4. doi: 10.1038/nature06866.
  43. Yoda A, Yoda Y, Chiaretti S, et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA. 2010;107(1):252–7. doi: 10.1073/pnas.0911726107.
  44. Mullighan CG, Zhang J, Kasper LH, et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature. 2011;471(7337):235–9. doi: 10.1038/nature09727.
  45. Van Vlierberghe P, Palomero T, Khiabanian H, et al. PHF6 mutations in T-cell acute lymphoblastic leukemia. Nat Genet. 2010;42(4):338–42. doi: 10.1038/ng.542.
  46. Coustan-Smith E, Mullighan CG, Onciu M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56. doi: 10.1016/S1470-2045(08)70314-0.
  47. Weng AP, Ferrando AA, Lee W, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269–71. doi: 10.1126/science.1102160.
  48. Гапонова Т.В., Менделеева Л.П., Мисюрин А.В. и др. Экспрессия опухолеассоциированных генов PRAME, WT1 и XIAP у больных множественной миеломой. Онкогематология. 2009;2:52–5. [Gaponova TV, Mendeleeva LP, Misyurin AV, et al. PRAME, WT1 and XIAP tumor-associated genes expression in multiple myeloma patients. Onkogematologiya. 2009;2:52–5. (In Russ)]
  49. Абраменко И.В., Белоус Н.И., Крячок И.А. и др. Экспрессия гена PRAME при множественной миеломе. Терапевтический архив. 2004;76(7):77–81. [Abramenko IV, Belous NI, Kryachok IA, et al. PRAME gene expression in multiple myeloma. Terapevticheskii arkhiv. 2004;76(7):77–81. (In Russ)]
  50. Мисюрин В.А. Аутосомные раково-тестикулярные гены. Российский биотерапевтический журнал. 2014;13(3):77–82. [Misyurin VA. Autosomal cancer-testis genes. Rossiiskii bioterapevticheskii zhurnal. 2014;13(3):77–82. (In Russ)]
  51. Мисюрин А.В. Основы молекулярной диагностики онкогематологических заболеваний. Российский биотерапевтический журнал. 2016;15(4):18–24. doi: 10.17650/1726-9784-2016-15-4-18-24. [Misyurin AV. Essentials of the molecular diagnosis of oncohematological diseases. Rossiysky bioterapevtichesky zhurnal. 2016;15(4):18–24. doi: 10.17650/1726-9784-2016-15-4-18-24. (In Russ)]

Молекулярно-генетические нарушения в патогенезе опухолей системы крови и соответствующие им изменения сигнальных систем клетки

Л.Р. Тилова1, А.В. Савинкова1, Е.М. Жидкова1,2, О.И. Борисова1,3, Т.И. Фетисов1,4, К.А. Кузин1, О.А. Власова1, А.С. Антипова3, О.Ю. Баранова3, К.И. Кирсанов1, Г.А. Белицкий1, М.Г. Якубовская1, Е.А. Лесовая1,5

1 НИИ канцерогенеза, ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Moсква, Российская Федерация, 115478

2 Московский технологический университет, пр-т Вернадского, д. 78, Москва, Российская Федерация, 119454

3 НИИ клинической онкологии, ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 23, Moсква, Российская Федерация, 115478

4 Первый Московский государственный медицинский университет им. И.М. Сеченова, ул. Трубецкая, д. 8, корп. 2, Москва, Российская Федерация, 119991

5 Рязанский государственный медицинский университет им. И.П. Павлова, ул. Высоковольтная, д. 9, Рязань, Российская Федерация, 390026

Для переписки: Екатерина Андреевна Лесовая, канд. биол. наук, Каширское ш., д. 24, стр. 15, Moсква, Российская Федерация, 115478; тел.: 8(910)471-41-28; e-mail: lesovenok@yandex.ru

Для цитирования: Тилова Л.Р., Савинкова А.В., Жидкова Е.М. и др. Молекулярно-генетические нарушения в патогенезе опухолей системы крови и соответствующие им изменения сигнальных систем клетки. Клиническая онкогематология. 2017;10(2):235–49.

DOI: 10.21320/2500-2139-2017-10-2-235-249


РЕФЕРАТ

Заболевания системы крови включают широкую группу злокачественных опухолей кроветворной и лимфоидной тканей, в основе патогенеза которых лежат генетические изменения, специфические для каждой отдельной разновидности нозологий. Одной из характерных особенностей онкогематологических заболеваний является высокая частота хромосомных аномалий (делеции, транслокации, инсерции). Кроме того, наблюдаются также мутации отдельных генов или блокирование нормальной регуляции функционирования генов в связи с эпигеномными событиями. Прогрессирование онкогематологических заболеваний может быть обусловлено накоплением различных генетических нарушений. Современная классификация опухолей кроветворной и лимфоидной тканей основана на анализе клинических данных, морфологических и функциональных признаков опухолевых клеток и выявлении специфических цитогенетических и молекулярно-генетических нарушений. К настоящему времени установлено большое количество генетических нарушений, характерных для конкретных типов злокачественных новообразований системы крови. Это позволяет оптимизировать лечебную тактику, а также разрабатывать, тестировать и вводить в клиническое использование ряд таргетных препаратов. К ним относятся препараты на основе моноклональных антител (ритуксимаб, алемтузумаб и др.), низкомолекулярные соединения (иматиниб, бортезомиб, карфилзомиб). Для разработки новых таргетных молекул или же перепрофилирования уже известных химиопрепаратов не только полезна информация об аномалиях при каждом типе гематологической опухоли, но и понимание изменений в эфферентных путях передачи сигнала в клетке, которые затрагивают данное нарушение. В настоящем обзоре рассматриваются генетические нарушения при заболеваниях, обозначенных в международной классификации ВОЗ опухолей кроветворной и лимфоидной тканей 2008 г. и дополненной в 2016 г., и соответствующие изменения в сигнальных путях, связанные со злокачественной трансформацией клеток кроветворной системы.

Ключевые слова: опухоли кроветворной и лимфоидной тканей, хромосомные аномалии, нарушения сигнальных путей, классификация ВОЗ.

Получено: 29 сентября 2016 г.

Принято в печать: 16 января 2017 г.

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ЛИТЕРАТУРА

  1. Van Etten RA. Aberrant cytokine signaling in leukemia. Oncogene. 2007;26(47):6738–49. doi: 10.1038/sj.onc.1210758.
  2. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110(4):1092–7. doi: 10.1182/blood-2007-04-083501.
  3. Jabbour EJ, Hughes TP, Cortes JE, et al. Potential mechanisms of disease progression and management of advanced-phase chronic myeloid leukemia. Leuk Lymphoma. 2014;55(7):1451–62. doi: 10.3109/10428194.2013.845883.
  4. Kota J, Caceres N, Constantinescu SN. Aberrant signal transduction pathways in myeloproliferative neoplasms. Leukemia. 2008;22(10):1828–40. doi: 10.1038/leu.2008.236.
  5. Tefferi A, Sirhan S, Lasho TL, et al. Concomitant neutrophil JAK2 mutation screening and PRV-1 expression analysis in myeloproliferative disorders and secondary polycythaemia. Br J Haematol. 2005;131(2):166–71. doi: 10.1111/j.1365–2141.2005.05743.x.
  6. Smalley KS, Sondak VK, Weber JS. c-KIT signaling as the driving oncogenic event in sub-groups of melanomas. Histol Histopathol. 2009;24(5):643–50. doi: 10.14670/HH-24.643.
  7. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117(19):5019–32. doi: 10.1182/blood-2011-01-293050.
  8. Копнин БП. Неопластическая клетка: основные свойства и механизмы их возникновения. Практическая онкология. 2002;3(4):229–35. [Kopnin BP. Neoplastic cell: principal characteristics and mechanisms of their development. Prakticheskaya onkologiya. 2002;3(4):229–35. (In Russ)]
  9. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. doi: 10.1182/blood-2016-03-643544.
  10. Bain BJ, Ahmad S. Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities? Br J Haematol. 2014;166(6):809–17. doi: 10.1111/bjh.1296.
  11. Surani MA, Hajkova P. Epigenetic reprogramming of mouse germ cells toward totipotency. Cold Spring Harb Symp Quant Biol. 2010;75:211–8. doi: 10.1101/sqb.2010.75.010.
  12. Carbuccia N, Murati A, Trouplin V, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia. 2009;23(11):2183–6. doi: 10.1038/leu.2009.141.
  13. Переводчикова Н.И., Горбунова, В.А. Руководство по химиотерапии опухолевых заболеваний, 4-е издание. Москва: Практическая медицина, 2015. [Perevodchikova NI, Gorbunova VA. Rukovodstvo po khimioterapii opukholevykh zabolevanii. (Guidelines for chemotherapy of tumors.) 4th edition. Moscow: Prakticheskaya meditsina Publ.; 2015. (In Russ)]
  14. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51. doi: 10.1182/blood-2009-03-209262.
  15. Riveiro-Falkenbach E, Soengas MS. Control of tumorigenesis and chemoresistance by the DEK oncogene. Clin Cancer Res. 2010;16(11):2932–8. doi: 10.1158/1078-0432.CCR-09-2330.
  16. Naoe T. Developing target therapy against oncogenic tyrosine kinase in myeloid maliganacies. Curr Pharm Biotechnol. 2006;7(5):331–7. doi: 10.2174/138920106778521514.
  17. Buonamici S, Chakraborty S, Senyuk V, et al. The role of EVI1 in normal and leukemic cells. Blood Cells Mol Dis. 2003;31(2):206–12. doi: 10.1016/S1079-9796(03)00159-1.
  18. O’Neil J, Calvo J, McKenna K, et al. Activating Notch1 mutations in mouse models of T-ALL. Blood. 2006;107(2):781–5. doi: 10.1182/blood-2005-06-2553.
  19. Williams JH, Daly LN, Ingley E, et al. HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1. EMBO J. 1999;18(20):5559–66. doi: 10.1093/emboj/18.20.5559.
  20. Rau R, Brown P. Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity. Hematol Oncol. 2009;27(4):171–81. doi: 10.1002/hon.904.
  21. Simon MC. Transcription factor GATA-1 and erythroid development. Proc Soc Exp Biol Med. 1993;202(2):115–21.
  22. Orkin SH, Shivdasani RA, Fujiwara Y, et al. Transcription factor GATA-1 in megakaryocyte development. Stem Cells. 1998;16(Suppl 2):79–83. doi: 10.1002/stem.5530160710.
  23. Shimizu R, Engel JD, Yamamoto M. GATA1-related leukaemias. Nat Rev Cancer. 2008;8(4):279–87. doi: 10.1038/nrc2348.
  24. Yoshida K, Toki T, Okuno Y, et al. The landscape of somatic mutations in Down syndrome-related myeloid disorders. Nat Genet. 2013;45(11):1293–9. doi: 10.1038/ng.2759.
  25. Coluccia AM, Vacca A, Dunach M, et al. Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation. EMBO J. 2007;26(5):1456–66. doi: 10.1038/sj.emboj.7601485.
  26. Sengupta A, Banerjee D, Chandra S, et al. Deregulation and cross talk among Sonic hedgehog, Wnt, Hox and Notch signaling in chronic myeloid leukemia progression. Leukemia. 2007;21(5):949–55. doi: 10.1038/sj.leu.240465.
  27. Sano H, Ohki K, Park MJ, et al. CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8;21). Br J Haematol. 2015;170(3):391–7. doi: 10.1111/bjh.13439.
  28. Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013;368(19):1781–90. doi: 10.1056/NEJMoa1214514.
  29. Tefferi A, Lasho TL, Abdel-Wahab O, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia. 2010;24(7):1302–9. doi: 10.1038/leu.2010.113.
  30. Barbui T, Thiele J, Vannucchi AM, et al. Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. Blood Cancer J. 2015;5(8):e337. doi: 10.1038/bcj.2015.64.
  31. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67. doi: 10.1016/j.ccr.2010.11.015.
  32. Patnaik MM, Tefferi A. Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia. Blood Cancer J. 2016;6(2):e393. doi: 10.1038/bcj.2016.5.
  33. Greenberger JS. Ras mutations in human leukemia and related disorders. Int J Cell Cloning. 1989;7(6):343–59. doi: 10.1002/stem.5530070603.
  34. Matynia AP, Szankasi P, Shen W, et al. Molecular genetic biomarkers in myeloid malignancies. Arch Pathol Lab Med. 2015;139(5):594–601. doi: 10.5858/arpa.2014-0096-RA.
  35. Fenaux P. Chromosome and molecular abnormalities in myelodysplastic syndromes. Int J Hematol. 2001;73(4):429–37. doi: 10.1007/bf02994004.
  36. Vallespi T, Imbert M, Mecucci C, et al. Diagnosis, classification, and cytogenetics of myelodysplastic syndromes. Haematologica. 1998;83(3):258–75.
  37. Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241–7. doi: 10.1038/leu.2013.336.
  38. Zahid MF, Patnaik MM, Gangat N, et al. Insight into the molecular pathophysiology of myelodysplastic syndromes: targets for novel therapy. Eur J Haematol. 2016;97(4):313–20. doi: 10.1111/ejh.12771.
  39. Griffiths EA, Gore SD, Hooker C, et al. Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation. Leuk Lymphoma. 2010;51(9):1711–9. doi: 10.3109/10428194.2010.496505.
  40. Niebuhr B, Fischer M, Tager M, et al. Gatekeeper function of the RUNX1 transcription factor in acute leukemia. Blood Cells Mol Dis. 2008;40(2):211–8. doi: 10.1016/j.bcmd.2007.07.018.
  41. Elagib KE, Goldfarb AN. Oncogenic pathways of AML1-ETO in acute myeloid leukemia: multifaceted manipulation of marrow maturation. Cancer Lett. 2007;251(2):179–86. doi: 10.1016/j.canlet.2006.10.010.
  42. Peterson LF, Zhang DE. The 8;21 translocation in leukemogenesis. Oncogene. 2004;23(24):4255–62. doi: 10.1038/sj.onc.1207727.
  43. Slattery ML, Lundgreen A, Herrick JS, et al. Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E and risk of colon and rectal cancer: additional support for a TGF-beta-signaling pathway. Carcinogenesis. 2011;32(3):318–26. doi: 10.1093/carcin/bgq245.
  44. Ma X, Renda MJ, Wang L, et al. Rbm15 modulates Notch-induced transcriptional activation and affects myeloid differentiation. Mol Cell Biol. 2007;27(8):3056–64. doi: 10.1128/MCB.01339-06.
  45. Feng Y, Bommer GT, Zhai Y, et al. Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. Cancer Res. 2007;67(2):482–91. doi: 10.1158/0008-5472.CAN-06-2314.
  46. Cornet E, Mossafa H, Courel K, et al. Persistent polyclonal binucleated B-cell lymphocytosis and MECOM gene amplification. BMC Res Notes. 2016;9(1):138. doi: 10.1186/s13104-015-1742-3.
  47. Yamazaki H, Suzuki M, Otsuki A, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25(4):415–27. doi: 10.1016/j.ccr.2014.02.008.
  48. Sato T, Goyama S, Nitta E, et al. Evi-1 promotes para-aortic splanchnopleural hematopoiesis through up-regulation of GATA-2 and repression of TGF-b signaling. Cancer Sci. 2008;99(7):1407–13. doi: 10.1111/j.1349-7006.2008.00842.x.
  49. Tokita K, Maki K, Mitani K. RUNX1/EVI1, which blocks myeloid differentiation, inhibits CCAAT-enhancer binding protein alpha function. Cancer Sci. 2007;98(11):1752–7. doi: 10.1111/j.1349-7006.2007.00597.x.
  50. Chandra P, Luthra R, Zuo Z, et al. Acute myeloid leukemia with t(9;11)(p21–22;q23): common properties of dysregulated ras pathway signaling and genomic progression characterize de novo and therapy-related cases. Am J Clin Pathol. 2010;133(5):686–93. doi: 10.1309/ajcpgii1tt4nyogi.
  51. Grimwade D, Gorman P, Duprez E, et al. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia. Blood. 1997;90(12):4876–85.
  52. Morgan RG, Pearn L, Liddiard K, et al. Gamma-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of beta-catenin. Leukemia. 2013;27(2):336–43. doi: 10.1038/leu.2012.221.
  53. Koschmieder S, Halmos B, Levantini E, et al. Dysregulation of the C/EBPalpha differentiation pathway in human cancer. J Clin Oncol. 2009;27(4):619–28. doi: 10.1200/JCO.2008.17.9812.
  54. Campidelli C, Agostinelli C, Stitson R, et al. Myeloid sarcoma: extramedullary manifestation of myeloid disorders. Am J Clin Pathol. 2009;132(3):426–37. doi: 10.1309/ajcp1za7hyzkazhs.
  55. Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992;80(4):879–86.
  56. Showe LC, Croce CM. The role of chromosomal translocations in B- and T-cell neoplasia. Annu Rev Immunol. 1987;5(1):253–77. doi: 10.1146/annurev.iy.05.040187.001345.
  57. Look AT. Oncogenic role of “master” transcription factors in human leukemias and sarcomas: a developmental model. Adv Cancer Res. 1995;67:25–57. doi: 10.1016/s0065-230x(08)60709-5.
  58. Sasaki K, Iwai K. Roles of linear ubiquitinylation, a crucial regulator of NF-kappaB and cell death, in the immune system. Immunol Rev. 2015;266(1):175–89. doi: 10.1111/imr.12308.
  59. Chiaretti S, Foa R. T-cell acute lymphoblastic leukemia. Haematologica. 2009;94(2):160–2. doi: 10.3324/haematol.2008.004150.
  60. Mullighan CG. The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematol Am Soc Hematol Educ Program. 2014;2014(1):174–80. doi: 10.1182/asheducation-2014.1.174.
  61. Pasqualucci L, Dalla-Favera R. The genetic landscape of diffuse large B-cell lymphoma. Semin Hematol. 2015;52(2):67–76. doi: 10.1053/j.seminhematol.2015.01.005.
  62. Noguchi M, Ropars V, Roumestand C, et al. Proto-oncogene TCL1: more than just a coactivator for Akt. FASEB J. 2007;21(10):2273–84. doi: 10.1096/fj.06-7684com.
  63. Liebisch P, Dohner H. Cytogenetics and molecular cytogenetics in multiple myeloma. Eur J Cancer. 2006;42(11):1520–9. doi: 10.1016/j.ejca.2005.12.028.
  64. Yanai S, Nakamura S, Takeshita M, et al. Translocation t(14;18)/IGH-BCL2 in gastrointestinal follicular lymphoma: correlation with clinicopathologic features in 48 patients. Cancer. 2011;117(11):2467–77. doi: 10.1002/cncr.25811.
  65. Flossbach L, Antoneag E, Buck M, et al. BCL6 gene rearrangement and protein expression are associated with large cell presentation of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Int J Cancer. 2011;129(1):70–7. doi: 10.1002/ijc.25663.
  66. Janz S. Myc translocations in B cell and plasma cell neoplasms. DNA Repair (Amst). 2006;5(9–10):1213–24. doi: 10.1016/j.dnarep.2006.05.017.
  67. Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17(2):215–20. doi: 10.1038/cdd.2009.69.
  68. Vermeer MH, van Doorn R, Dijkman R, et al. Novel and highly recurrent chromosomal alterations in Sezary syndrome. Cancer Res. 2008;68(8):2689–98. doi: 10.1158/0008-5472.CAN-07-6398.
  69. Herling M, Patel KA, Teitell MA, et al. High TCL1 expression and intact T-cell receptor signaling define a hyperproliferative subset of T-cell prolymphocytic leukemia. Blood. 2008;111(1):328–37. doi: 10.1182/blood-2007-07-101519.
  70. Joiner M, Le Toriellec E, Despouy G, et al. The MTCP1 oncogene modifies T-cell homeostasis before leukemogenesis in transgenic mice. Leukemia. 2007;21(2):362–6. doi: 10.1038/sj.leu.2404476.
  71. Laine J, Kunstle G, Obata T, et al. The protooncogene TCL1 is an Akt kinase coactivator. Mol Cell. 2000;6(2):395–407. doi: 10.1016/S1097-2765(00)00039-3.
  72. Mosse CA, Stumph JR, Best DH, et al. A B-cell lymphoma diagnosed in “floater” tissue: implications of the diagnosis and resolution of a laboratory error. Am J Med Sci. 2009;338(3):248–51. doi: 10.1097/MAJ.0b013e3181a88dc.
  73. Roukos V, Mathas S. The origins of ALK translocations. Front Biosci. 2015;7(2):260–8. doi: 10.2741/s439.
  74. Re D, Zander T, Diehl V, Wolf J. Genetic instability in Hodgkin’s lymphoma. Ann Oncol. 2002;13(Suppl 1):19–22. doi: 10.1093/annonc/13.s1.19.
  75. Suvajdzic N, Djurdjevic P, Todorovic M, et al. Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of systemic autoimmune diseases. Med Oncol. 2012;29(3):2207–11. doi: 10.1007/s12032-011-0022-x.
  76. Roberts KG, Pei D, Campana D, et al. Outcomes of children with BCR-ABL1-like acute lymphoblastic leukemia treated with risk-directed therapy based on the levels of minimal residual disease. J Clin Oncol. 2014;32(27):3012–20. doi: 10.1200/JCO.2014.55.4105.
  77. Zweidler-McKay PA, Pear WS. Notch and T cell malignancy. Semin Cancer Biol. 2004;14(5):329–40. doi: 10.1016/j.semcancer.2004.04.012.
  78. Atlas of Genetics and Cytogenetics in Oncology and Haematology. [Internet] Available from: http://www.atlasgeneticsoncology.org/ (accessed 13.03.2017).
  79. Lu D, Zhao Y, Tawatao R, et al. Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2004;101(9):3118–23. doi: 10.1073/pnas.0308648100.
  80. Rahmatpanah FB, Carstens S, Hooshmand SI, et al. Large-scale analysis of DNA methylation in chronic lymphocytic leukemia. Epigenomics. 2009;1(1):39–61. doi: 10.2217/epi.09.10.
  81. Dungarwalla M, Appiah-Cubi S, Kulkarni S, et al. High-grade transformation in splenic marginal zone lymphoma with circulating villous lymphocytes: the site of transformation influences response to therapy and prognosis. Br J Haematol. 2008;143(1):71–4. doi: 10.1111/j.1365-2141.2008.07301.x.
  82. Neurath MF, Stuber ER, Strober W. BSAP: a key regulator of B-cell development and differentiation. Immunol Today. 1995;16(12):564–9. doi: 10.1016/0167-5699(95)80078-6.
  83. Bench AJ, Erber WN, Follows GA, et al. Molecular genetic analysis of haematological malignancies II: Mature lymphoid neoplasms. Int J Lab Hematol. 2007;29(4):229–60. doi: 10.1111/j.1751-553X.2007.00876.x.
  84. Brito JL, Walker B, Jenner M, et al. MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells. Haematologica. 2009;94(1):78–86. doi: 10.3324/haematol.13426.
  85. Aamot HV, Bjornslett M, Delabie J, et al. t(14;22)(q32;q11) in non-Hodgkin lymphoma and myeloid leukaemia: molecular cytogenetic investigations. Br J Haematol. 2005;130(6):845–51. doi: 10.1111/j.1365-2141.2005.05688.x.
  86. Arcaini L, Lucioni M, Boveri E, et al. Nodal marginal zone lymphoma: current knowledge and future directions of an heterogeneous disease. Eur J Haematol. 2009;83(3):165–74. doi: 10.1111/j.1600-0609.2009.01301.x.
  87. Du MQ. MALT lymphoma: recent advances in aetiology and molecular genetics. J Clin Exp Hematop. 2007;47(2):31–42. doi: 10.3960/jslrt.47.31.
  88. Mateo M, Mollejo M, Villuendas R, et al. 7q31–32 allelic loss is a frequent finding in splenic marginal zone lymphoma. Am J Pathol. 1999;154(5):1583–9. doi: 10.1016/S0002-9440(10)65411-9.
  89. Shimada K, Kinoshita T, Naoe T, et al. Presentation and management of intravascular large B-cell lymphoma. Lancet Oncol. 2009;10(9):895–902. doi: 10.1016/S1470-2045(09)70140-8.
  90. Bogusz AM, Seegmiller AC, Garcia R, et al. Plasmablastic lymphomas with MYC/IgH rearrangement: report of three cases and review of the literature. Am J Clin Pathol. 2009;132(4):597–605. doi: 10.1309/ajcpfur1bk0uodts.
  91. Weerkamp F, van Dongen JJ, Staal FJ. Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia. Leukemia. 2006;20(7):1197–205. doi: 10.1038/sj.leu.2404255.
  92. Zhang D, Loughran TP, Jr. Large granular lymphocytic leukemia: molecular pathogenesis, clinical manifestations, and treatment. Hematol Am Soc Hematol Educ Program. 2012;2012:652–9. doi: 10.1182/asheducation-2012.1.652.
  93. Lima M. Aggressive mature natural killer cell neoplasms: from epidemiology to diagnosis. Orphanet J Rare Dis. 2013;8(1):95. doi: 10.1186/1750-1172-8-95.
  94. Ohshima K. Molecular Pathology of Adult T-Cell Leukemia/Lymphoma. Oncology. 2015;89(Suppl 1):7–15. doi: 10.1159/000431058.
  95. Finalet Ferreiro J, Rouhigharabaei L, Urbankova H, et al. Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. PLoS One. 2014;9(7):e102977. doi: 10.1371/journal.pone.0102977.
  96. Ferreri AJ, Govi S, Pileri SA. Hepatosplenic gamma-delta T-cell lymphoma. Crit Rev Oncol Hematol. 2012;83(2):283–92. doi: 10.1016/j.critrevonc.2011.10.001.
  97. Devata S, Wilcox RA. Cutaneous T-Cell Lymphoma: A Review with a Focus on Targeted Agents. Am J Clin Dermatol. 2016;17(3):225–37. doi: 10.1007/s40257-016-0177-5.
  98. da Silva Almeida AC, Abate F, Khiabanian H, et al. The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome. Nat Genet. 2015;47(12):1465–70. doi: 10.1038/ng.3442.
  99. Izykowska K, Przybylski GK. Genetic alterations in Sezary syndrome. Leuk Lymphoma. 2011;52(5):745–53. doi: 10.3109/10428194.2010.551159.
  100. Wang SA, Hasserjian RP. Acute Erythroleukemias, Acute Megakaryoblastic Leukemias, and Reactive Mimics: A Guide to a Number of Perplexing Entities. Am J Clin Pathol. 2015;144(1):44–60. doi: 10.1309/ajcprkyat6ezqhc7.
  101. Nicolay JP, Felcht M, Schledzewski K, et al. Sezary syndrome: old enigmas, new targets. J Dtsch Dermatol Ges. 2016;14(3):256–64. doi: 10.1111/ddg.12900.
  102. Pletneva MA, Smith LB. Anaplastic large cell lymphoma: features presenting diagnostic challenges. Arch Pathol Lab Med. 2014;138(10):1290–4. doi: 10.5858/arpa.2014-0295-CC.
  103. Ondrejka SL, Hsi ED. T-cell Lymphomas: Updates in Biology and Diagnosis. Surg Pathol Clin. 2016;9(1):131–41. doi: 10.1016/j.path.2015.11.002.
  104. Churchill H, Naina H, Boriack R, et al. Discordant intracellular and plasma D-2-hydroxyglutarate levels in a patient with IDH2 mutated angioimmunoblastic T-cell lymphoma. Int J Clin Exp Pathol. 2015;8(9):11753–9.
  105. Sakata-Yanagimoto M, Enami T, Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5. doi: 10.1038/ng.2872.
  106. Feldman AL, Dogan A, Smith DI, et al. Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood. 2011;117(3):915–9. doi: 10.1182/blood-2010-08-303305.
  107. Persad P, Pang CS. Composite ALK-negative anaplastic large cell lymphoma and small lymphocytic lymphoma involving the right inguinal lymph node. Pathol Res Pract. 2014;210(2):127–9. doi: 10.1016/j.prp.2013.09.006.
  108. Kikuma K, Yamada K, Nakamura S, et al. Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. Hum Pathol. 2014;45(6):1276–84. doi: 10.1016/j.humpath.2013.10.038.
  109. Djeu JY, Wei S. Clusterin and chemoresistance. Adv Cancer Res. 2009;105:77–92. doi: 10.1016/S0065-230X(09)05005-2.
  110. Sun W, Nordberg ML, Fowler MR. Histiocytic sarcoma involving the central nervous system: clinical, immunohistochemical, and molecular genetic studies of a case with review of the literature. Am J Surg Pathol. 2003;27(2):258–65. doi: 10.1097/00000478-200302000-00017.
  111. Scappaticci S, Danesino C, Rossi E, et al. Cytogenetic abnormalities in PHA-stimulated lymphocytes from patients with Langerhans cell histocytosis. AIEOP-Istiocitosi Group. Br J Haematol. 2000;111(1):258–62. doi: 10.1111/j.1365-2141.2000.02313.x.
  112. Arico M, Danesino C. Langerhans’ cell histiocytosis: is there a role for genetics? Haematologica. 2001;86(10):1009–14.
  113. Nakayama M, Takahashi K, Hori M, et al. Langerhans cell sarcoma of the cervical lymph node: a case report and literature review. Auris Nasus Larynx. 2010;37(6):750–3. doi: 10.1016/j.anl.2010.04.007.
  114. Takahashi E, Nakamura S. Histiocytic sarcoma: an updated literature review based on the 2008 WHO classification. J Clin Exp Hematopathol. 2013;53(1):1–8. doi: 10.3960/jslrt.53.1.
  115. Pettigrew HD, Teuber SS, Kong JS, et al. Contemporary challenges in mastocytosis. Clin Rev Allergy Immunol. 2010;38(2–3):125–34. doi: 10.1007/s12016-009-8164-8.
  116. Chatterjee A, Ghosh J, Kapur R. Mastocytosis: a mutated KIT receptor induced myeloproliferative disorder. Oncotarget. 2015;6(21):18250–64. doi: 10.18632/oncotarget.4213.
  117. Kairouz S, Hashash J, Kabbara W, et al. Dendritic cell neoplasms: an overview. Am J Hematol. 2007;82(10):924–8. doi: 10.1002/ajh.20857.
 

Цитогенетические и молекулярно-генетические факторы прогноза острых миелоидных лейкозов

А.В. Мисюрин

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Moсква, Российская Федерация, 115478

Для переписки: Андрей Витальевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; e-mail: and@genetechnology.ru

Для цитирования: Мисюрин А.В. Цитогенетические и молекулярно-генетические факторы прогноза острых миелоидных лейкозов. Клиническая онкогематология. 2017;10(2):227–34.

DOI: 10.21320/2500-2139-2017-10-2-227-234


РЕФЕРАТ

В обзоре приведены данные о диагностическом и прогностическом значении цитогенетических и молекулярно-генетических маркеров острых миелоидных лейкозов (ОМЛ). Показано, что в ряде случаев выделенные ранее на основе клинико-морфоцитохимических характеристик варианты ОМЛ можно разграничить благодаря обнаружению специфических генетических и хромосомных дефектов. Тем не менее, некоторые одинаковые повторяющиеся хромосомные аномалии могут быть обнаружены у больных ОМЛ, заболевание у которых согласно клинико-морфоцитохимическим признакам можно отнести к разным вариантам миелоидного лейкоза. В настоящее время признается, что изменение кариотипа является определяющим фактором прогноза, имеющим более существенное значение, чем критерии, основанные на морфологических и цитохимических признаках. В связи с этим выбор риск-адаптированной программы лечения ОМЛ следует проводить с учетом результатов цитогенетического исследования. В обзоре особый раздел посвящен известным к настоящему времени мутациям генов, которые могут влиять на результаты лечения ОМЛ.

Ключевые слова: ОМЛ, хромосомная аномалия, химерный онкоген, экспрессия гена, мутация гена.

Получено: 16 сентября 2016 г.

Принято в печать: 3 января 2017 г.

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ЛИТЕРАТУРА

  1. Гематология: национальное руководство. Под ред. О.А. Рукавицына. М.: ГЭОТАР-Медиа, 2015. 776 с. [Rukavitsyn OA, ed. Gematologiya: natsional’noe rukovodstvo. (Hematology: national guidelines.) Moscow: GEOTAR-Media Publ.; 2015. 776 p. (In Russ)]
  2. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  3. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51. doi: 10.1182/blood-2009-03-209262.
  4. Zerbini MCN, Soares FA, Velloso EDRP, et al. World Health Organization classification of tumors of hematopoietic and lymphoid tissues, 2008: major changes from the 3rd edition. Revista da Associacao Medica Brasileira. 2011;57(1): 6–73. doi: 10.1590/S0104-42302011000100019.
  5. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451–8. doi: 10.1111/j.1365-2141.1976.tb03563.
  6. Kuhnl A, Grimwade D. Molecular markers in acute myeloid leukaemia. Int J Hematol. 2012;96(2):153–63. doi: 10.1007/s12185-012-1123-9.
  7. Burnett AK, Wheatley K, Goldstone AH, et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol. 2002;118(2):385–400. doi: 10.1046/j.1365-2141.2002.03724.x.
  8. Cornelissen JJ, van Putten WL, Verdonck LF, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109(9):3658–66. doi: 10.1182/blood-2006-06-025627.
  9. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96(13):4075–83.
  10. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–65. doi: 10.1182/blood-2009-11-254441.
  11. Blum W, Mrozek K, Ruppert AS, et al. Adult de novo acute myeloid leukemia with t(6;11)(q27;q23): results from Cancer and Leukemia Group B Study 8461 and review of the literature. Cancer. 2005;103(6):1316. doi: 10.1002/cncr.20931
  12. Krauter J, Wagner K, Schafer I, et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2009;27(18):3000–6. doi: 10.1200/jco.2008.16.7981.
  13. von Neuhoff C, Reinhardt D, Sander A, et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol. 2010;28(16):2682–9. doi: 10.1200/JCO.2009.25.6321.
  14. Rucker FG, Bullinger L, Schwaenen C, et al. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol. 2006;24(24):3887–94. doi: 10.1200/jco.2005.04.5450.
  15. Mrozek K. Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype. Semin Oncol. 2008;35(4):365–77. doi: 10.1053/j.seminoncol.2008.04.007.
  16. Breems DA, Van Putten WL, De Greef GE, et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol. 2008;26(29):4791–7. doi: 10.1200/JCO.2008.16.0259.
  17. Smith ML, Hills RK, Grimwade D. Independent prognostic variables in acute myeloid leukaemia. Blood Rev. 2011;25(1):39–51. doi: 10.1016/j.blre.2010.10.002.
  18. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301. doi: 10.1056/NEJMoa0810069.
  19. Metzeler KH, Maharry K, Radmacher MD, et al. TET2 mutations improve the new European LeukemiaNet risk classification of acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2011;29(10):1373–81. doi: 10.1200/JCO.2010.32.7742.
  20. Chou WC, Chou SC, Liu CY, et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood. 2011;118(14):3803–10. doi: 10.1182/blood-2011-02-339747.
  21. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058–66.
  22. Thol F, Damm F, Wagner K, et al. Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood. 2010(4);116:614–6. doi: 10.1182/blood-2010-03-272146.
  23. Chou WC, Hou HA, Chen CY, et al. Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation. Blood. 2010;115(14):2749–54. doi: 10.1182/blood-2009-11-253070.
  24. Marcucci G, Maharry K, Wu YZ, et al. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol. 2010;28(14):2348–55. doi: 10.1200/jco.2009.27.3730.
  25. Paschka P, Schlenk RF, Gaidzik VI, et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol. 2010;28(22):3636–43. doi: 10.1200/jco.2010.28.3762.
  26. Schnittger S, Haferlach C, Ulke M, et al. IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status. Blood. 2010;116(25):5486–96. doi: 10.1182/blood-2010-02-267955.
  27. Ravandi F, Patel K, Luthra R, et al. Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin. Cancer. 2012;118(10):2665–73. doi: 10.1002/cncr.26580.
  28. Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424–33. doi: 10.1056/NEJMoa1005143.
  29. Thol F, Damm F, Ludeking A, et al. Incidence and prognostic influence of DNMT3A mutations in acute myeloid leukemia. J Clin Oncol. 2011;29:2889–96. doi: 10.1200/JCO.2011.35.4894.
  30. Shen Y, Zhu YM, Fan X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood. 2011;118(20):5593–603. doi: 10.1182/blood-2011-03-343988.
  31. Hou HA, Kuo YY, Liu CY, et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood. 2011(2);119:559–68. doi: 10.1182/blood-2011-07-369934.
  32. Renneville A, Boissel N, Nibourel O, et al. Prognostic significance of DNA methyltransferase 3A mutations in cytogenetically normal acute myeloid leukemia: a study by the Acute Leukemia French Association. Leukemia. 2012;26(6):1247–54. doi: 10.1038/leu.2011.382.
  33. Marcucci G, Metzeler KH, Schwind S, et al. Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol. 2012;30(7):742–50. doi: 10.1200/jco.2011.39.2092.
  34. Markova J, Michkova P, Burckova K, et al. Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia. Eur J Haematol. 2012;88(2):128–35. doi: 10.1111/j.1600-0609.2011.01716.x.
  35. King-Underwood L, Renshaw J, Pritchard-Jones K. Mutations in the Wilms’ tumor gene WT1 in leukemias. Blood. 1996;87(6):2171–9.
  36. Virappane P, Gale R, Hills R, et al. Mutation of the Wilms’ tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype acute myeloid leukemia: the United Kingdom Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2008;26(33):5429–35. doi: 10.1200/jco.2008.16.0333.
  37. Paschka P, Marcucci G, Ruppert AS, et al. Wilms’ tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. J Clin Oncol. 2008;26(28):4595–602. doi: 10.1200/JCO.2007.15.2058.
  38. Boissel N, Leroy H, Brethon B, et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia. 2006;20(6):965–70. doi: 10.1038/sj.leu.2404188.
  39. Paschka P, Marcucci G, Ruppert AS, et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol. 2006;24(24):3904–11. doi: 10.1200/JCO.2006.06.9500.
  40. Cairoli R, Beghini A, Grillo G, et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood. 2006;107(9):3463–8. doi: 10.1182/blood-2005-09-3640.
  41. Schnittger S, Kohl TM, Haferlach T, et al. KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood. 2006;107(5):1791–9. doi: 10.1182/blood-2005-04-1466.
  42. Gelsi-Boyer V, Trouplin V, Adelaide J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145(6):788–800. doi: 10.1111/j.1365-2141.2009.07697.x.
  43. Chou WC, Huang HH, Hou HA, et al. Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations. Blood. 2010;116(20):4086–94. doi: 10.1182/blood-2010-05-283291.
  44. Metzeler KH, Becker H, Maharry K, et al. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. Blood. 2011;118(26):6920–9. doi: 10.1182/blood-2011-08-368225.
  45. Pratcorona M, Abbas S, Sanders MA, et al. Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. Haematologica. 2012;97(3):388–92. doi: 10.3324/haematol.2011.051532.
  46. Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079–89. doi: 10.1056/NEJMoa1112304.
  47. Grossmann V, Tiacci E, Holmes AB, et al. Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype. Blood. 2011;118(23):6153–63. doi: 10.1182/blood-2011-07-365320.
  48. Li M, Collins R, Jiao Y, et al. Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia. Blood. 2011;118(22):5914–7. doi: 10.1182/blood-2011-05-356204.
  49. Van Vlierberghe P, Patel J, Abdel-Wahab O, et al. PHF6 mutations in adult acute myeloid leukemia. Leukemia. 2011;25(1):130–4. doi: 10.1038/leu.2010.247.
  50. Mano H. Stratification of acute myeloid leukemia based on gene expression profiles. Int J Hematol. 2004;80(5):389–94. doi: 10.1532/ijh97.04111.
  51. Marcucci G, Mrozek K, Radmacher MD, et al. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood. 2011;117(4):1121–9. doi: 10.1182/blood-2010-09-191312.
  52. Smith ML, Hills RK, Grimwade D. Independent prognostic variables in acute myeloid leukaemia. Blood Rev. 2011;25(1):39–51. doi: 10.1016/j.blre.2010.10.002.
  53. Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005;352(3):254–66. doi: 10.1056/NEJMoa041974.
  54. Dohner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106(12):3740–6. doi: 10.1182/blood-2005-05-2164.
  55. Thiede C, Creutzig E, Illmer T, et al. Rapid and sensitive typing of NPM1 mutations using LNA-mediated PCR clamping. Leukemia. 2006;20(10):1897–9. doi: 10.1038/sj.leu.2404367.
  56. Schlenk RF, Dohner K, Krauter J, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1909–18. doi: 10.1056/NEJMoa074306.
  57. Green CL, Koo KK, Hills RK, et al. Prognostic significance of CEBPA mutations in a large cohort of younger adult patients with acute myeloid leukemia: impact of double CEBPA mutations and the interaction with FLT3 and NPM1 mutations. J Clin Oncol. 2010;28(16):2739–47. doi: 10.1200/JCO.2009.26.2501.
  58. Grisendi S, Mecucci C, Falini B, et al. Nucleophosmin and cancer. Nat Rev Cancer. 2006;6(7):493–505. doi: 10.1038/nrc1885.
  59. Freeman SD, Jovanovic JV, Grimwade D. Development of minimal residual disease-directed therapy in acute myeloid leukemia. Semin Oncol. 2008;35(4):388–400. doi: 10.1053/j.seminoncol.2008.04.009.
  60. Nakao M, Yokota S, Iwai T, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10(12):1911–8.
  61. Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98(6):1752–9. doi: 10.1182/blood.V98.6.1752.
  62. Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99(12):4326–35. doi: 10.1182/blood.V99.12.4326.
  63. Yanada M, Matsuo K, Suzuki T, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia. 2005;19(8):1345–9. doi: 10.1038/sj.leu.2403838.
  64. Mead AJ, Linch DC, Hills RK, et al. FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients. Blood. 2007;110(4):1262–70. doi: 10.1182/blood-2006-04-015826.
  65. Bacher U, Haferlach C, Kern W, et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients. Blood. 2008;111(5):2527–37. doi: 10.1182/blood-2007-05-091215.
  66. Whitman SP, Ruppert AS, Radmacher MD, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood. 2008;111(3):1552–9. doi: 10.1182/blood-2007-08-107946.
  67. Gale RE, Hills R, Pizzey AR, et al. Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood. 2005;106(12):3768–76. doi: 10.1182/blood-2005-04-1746.
  68. Souza Melo CP, Campos CB, Dutra AP, et al. Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias. Leuk Res. 2015;39(2):131–7. doi: 10.1016/j.leukres.2014.11.010.
  69. Cicconi L, Divona M, Ciardi C, et al. PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy. Leukemia. 2016;30(10):1987–92. doi: 10.1038/leu.2016.122.
  70. Radomska HS, Huettner CS, Zhang P, et al. CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors. Mol Cell Biol. 1998;18(7):4301–14. doi: 10.1128/mcb.18.7.4301.
  71. Pabst T, Mueller BU, Zhang P, et al. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet. 2001;27(3):263–70. doi: 10.1038/85820.
  72. Smith ML, Cavenagh JD, Lister TA, et al. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med. 2004;351(23):2403–7. doi: 10.1056/NEJMoa041331.
  73. Pabst T, Eyholzer M, Fos J, et al. Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis. Br J Cancer. 2009;100(8):1343–6. doi: 10.1038/sj.bjc.6604977.
  74. Kirstetter P, Schuster MB, Bereshchenko O, et al. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell. 2008;13(4):299–310. doi: 10.1016/j.ccr.2008.02.008.
  75. Wouters BJ, Lowenberg B, Erpelinck-Verschueren CA, et al. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113(13):3088–91. doi: 10.1182/blood-2008-09-179895.
  76. Taskesen E, Bullinger L, Corbacioglu A, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011;117(8):2469–75. doi: 10.1182/blood-2010-09-307280.
  77. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74. doi: 10.1182/blood-2009-07-235358.
  78. Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–3. doi: 10.1126/science.1210597.
  79. Abdel-Wahab O, Mullally A, Hedvat C, et al. Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009;114(1):144–7. doi: 10.1182/blood-2009-03-210039.
  80. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553–67. doi: 10.1016/j.ccr.2010.11.015.
  81. Ko M, Huang Y, Jankowska AM, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839–43. doi: 10.1038/nature09586.
  82. Langemeijer SM, Kuiper RP, Berends M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41(7):838–42. doi: 10.1038/ng.391.
  83. Jankowska AM, Szpurka H, Tiu RV, et al. Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009;113(25):6403–10. doi: 10.1182/blood-2009-02-205690.
  84. Gaidzik VI, Paschka P, Spath D, et al. TET2 mutations in acute myeloid leukemia (AML): results from a comprehensive genetic and clinical analysis of the AML Study Group. J Clin Oncol. 2012;30(12):1350–7. doi: 10.1200/JCO.2011.39.2886.
  85. Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell. 2010;17(3):225–34. doi: 10.1016/j.ccr.2010.01.020.
  86. Gross S, Cairns RA, Minden MD, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010;207(2):339–44. doi: 10.1084/jem.20092506.
  87. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875–91. doi: 10.1182/blood-2008-04-150250.
  88. Diehl F, Rossig L, Zeiher AM, et al. The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood. 2007;109(4):1472–8. doi: 10.1182/blood-2006-08-039651.
  89. Li Y, Han J, Zhang Y, et al. Structural basis for activity regulation of MLL family methyltransferases. Nature. 2016;530(7591):447–52. doi: 10.1038/nature16952.
  90. Bower M, Parry P, Carter M, et al. Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5. Blood. 1994;84(11):3776–80.
  91. Schichman SA, Caligiuri MA, Strout MP, et al. ALL-1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements. Cancer Res. 1994;54(16):4277–80.
  92. Caligiuri MA, Schichman SA, Strout MP, et al. Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations. Cancer Res. 1994;54(2):370–3.
  93. Park JP, Ladd SL, Ely P, et al. Amplification of the MLL region in acute myeloid leukemia. Cancer Genet Cytogenet. 2000;121(2):198–205. doi: 10.1016/S0165-4608(00)00256-9.
  94. Schnittger S, Kinkelin U, Schoch C, et al. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia. 2000;14(5):796–804. doi: 10.1038/sj.leu.2401773.
  95. Slovak ML, Traweek ST, Willman CL, et al. Trisomy 11: an association with stem/progenitor cell immunophenotype. Br J Haematol. 1995;90(2):266–73. doi: 10.1111/j.1365-2141.1995.tb05146.x.
  96. Strout MP, Marcucci G, Bloomfield CD, et al. The partial tandem duplication of ALL1 (MLL) is consistently generated by Alu-mediated homologous recombination in acute myeloid leukemia. Proc Natl Acad Sci USA. 1998;95(5):2390–5. doi: 10.1073/pnas.95.5.2390.
  97. Klymenko S, Bebeshko V, Bazyka D, et al. AML1 gene rearrangements and mutations in radiation-associated acute myeloid leukemia and myelodysplastic syndromes. J Rad Res. 2005;46(2):249–55. doi: 10.1269/jrr.46.249.
  98. Мисюрин В.А., Лукина А.Е., Мисюрин А.В. и др. Особенности соотношения уровней экспрессии генов PRAME и PML/RARA в дебюте острого промиелоцитарного лейкоза. Российский биотерапевтический журнал. 2014;13(1):9–16. [Misyurin VA, Lukina AE, Misyurin AV. A ratio between gene expression levels of PRAME and PML/RARA at the onset of acute promyelocytic leukemia and clinical features of the disease. Rossiiskii bioterapevticheskii zhurnal. 2014;13(1):9–16. (In Russ)]
  99. Мисюрин А.В. Основы молекулярной диагностики онкогематологических заболеваний. Российский биотерапевтический журнал. 2016;15(4):18–24. doi: 10.17650/1726-9784-2016-15-4-18-24. [Misyurin AV. Fundamentals of the molecular diagnosis of oncohematological diseases. Rossiiskii bioterapevticheskii zhurnal. 2016;15(4):18–24. doi: 10.17650/1726-9784-2016-15-4-18-24. (In Russ)]

Миелоидные супрессорные клетки при некоторых онкогематологических заболеваниях

А.В. Пономарев

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Moсква, Российская Федерация, 115478

Для переписки: Александр Васильевич Пономарев, аспирант, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; e-mail: kl8546@yandex.ru

Для цитирования: Пономарев А.В. Миелоидные супрессорные клетки при некоторых онкогематологических заболеваниях. Клиническая онкогематология. 2017;10(1):29–38.

DOI: 10.21320/2500-2139-2017-10-1-29-38


РЕФЕРАТ

Миелоидные супрессорные клетки — это незрелые клетки миелоидного происхождения, обладающие иммуносупрессивными свойствами. В обзоре приведена характеристика миелоидных супрессорных клеток, в т. ч. варианты фенотипа, механизмы супрессивного воздействия на иммунную систему, механизмы рекрутирования опухолью миелоидных супрессоров. Дано краткое описание работ, в которых исследовались миелоидные супрессоры при онкогематологических заболеваниях, включая множественную миелому, лимфомы и лейкозы.

Ключевые слова: миелоидные супрессоры, супрессорные клетки миелоидного происхождения, множественная миелома, лимфомы, лейкозы.

Получено: 8 сентября 2016 г.

Принято в печать: 3 декабря 2016 г.

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ЛИТЕРАТУРА

  1. Тупицына Д.Н., Ковригина А.М., Тумян Г.С. и др. Клиническое значение внутриопухолевых FOXP3+ Т-регуляторных клеток при солидных опухолях и фолликулярных лимфомах: обзор литературы и собственные данные. Клиническая онкогематология. 2012;(5)3:193–203. [Tupitsyna DN, Kovrigina AM, Tumian GS, et al. Different clinical meaning of intratumoral FOXP3+ T-regulatory cells in solid tumors and follicular lymphomas: literature review and own data. Klinicheskaya onkogematologiya. 2012;(5)3:193–203. (In Russ)]
  2. Кадагидзе З.Г., Черткова А.И., Славина Е.Г. NKT-клетки и противоопухолевый иммунитет. Российский биотерапевтический журнал. 2011;10(3):9–16. [Kadagidze ZG, Chertkova AI, Slavina EG. NKT-cells and antitumor immunity. Rossiiskii bioterapevticheskii zhurnal. 2011;10(3):9–16. (In Russ)]
  3. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev 2012;12(4):253–68. doi: 10.1038/nri3175.
  4. Gabrilovich DI, Bronte V, Chen S-H, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007;67(1):425– doi: 10.1158/0008-5472.CAN-06-3037.
  5. Bowen JL, Olson JK. Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler’s virus-induced demyelinating disease. J Immunol. 2009;183(11):6971–80. doi: 10.4049/jimmunol.0902193.
  6. Tsiganov EN, Verbina EM, Radaeva TV, et al. Gr-1dim CD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J Immunol. 2014;192(10):4718–27. doi: 10.4049/jimmunol.1301365.
  7. Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007;204(6):1463–74.
  8. Гапонов М.А., Хайдуков С.В., Писарев В.М. и др. Субпопуляционная гетерогенность миелоидных иммуносупрессорных клеток у пациентов с септическими состояниями. Российский иммунологический журнал. 2015;9(18):11–14. [Gaponov MA, Khaidukov SV, Pisarev VM, et al. Subpopulation heterogeneity of immunosuppressive myeloid cells in patients with sepsis. Rossiiskii immunologicheskii zhurnal. 2015;9(18):11–14. (In Russ)]
  9. Makarenkova VP, Bansal V, Matta BM, et al. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176(4):2085–94. doi: 10.4049/jimmunol.176.4.2085.
  10. Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. Int. 2011;11(7):802–7. doi: 10.1016/j.intimp.2011.01.003.
  11. Diaz-Montero CM, Salem ML, Nishimura MI, et al. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49–59. doi: 10.1007/s00262-008-0523-
  12. Yazdani Y, Mohammadnia-Afrouzi M, Yousefi M, et al. Myeloid-derived suppressor cells in B cell malignancies. Tumour Biol. 2015;36(10):7339–53. doi: 10.1007/s13277-015-4004-z.
  13. Пономарев А.В. Миелоидные супрессорные клетки: общая характеристика. Иммунология. 2016;37(1):47–50. doi: 10.18821/0206-4952-2016-37-1-47-50. [Ponomarev AV. Myeloid suppressor cells: general characteristics. Immunologiya. 2016;37(1):47–50. doi: 10.18821/0206-4952-2016-37-1-47- (In Russ)]
  14. Gabrilovich DI, Nagaraj S. Myeloid-derived-suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74. doi: 10.1038/nri2506.
  15. Lechner MG, Megiel C, Russell SM, et al. Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl 2011;9(1):90. doi: 10.1186/1479-5876-9-90.
  16. Rodriguez PC, Ernstoff MS, Hernandez C, et al. Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes. Cancer Res. 2009;69(4):1553–60.
  17. Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res. 2001;61(12):4756–60.
  18. Youn J-I, Collazo M, Shalova I, et al. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leuk 2012;91(1):167–81. doi: 10.1189/jlb.0311177.
  19. Youn J-I, Nagaraj S, Collazo M, et al. Subsets of Myeloid-Derived Suppressor Cells in Tumor Bearing Mice. J Immunol. 2008;181(8):5791–802. doi: 10.4049/jimmunol.181.8.5791.
  20. Corzo CA, Condamine T, Lu L, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207(11):2439–53. doi: 10.1084/jem.20100587.
  21. Yang L, DeBusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell. 2004;6(4):409–21. doi: 10.1016/j.ccr.2004.08.031.
  22. Zhuang J, Zhang J, Lwin ST, et al. Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+ myeloid-derived suppressor cells. PLoS One. 2012;7(11):e48871. doi: 1371/journal.pone.0048871.
  23. Choi J, Suh B, Ahn YO, et al. CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function. Tumour Biol. 2012;33(1):121–9. doi: 10.1007/s13277-011-0254-
  24. Stanojevic I, Miller K, Kandolf-Sekulovic L, et al. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma. Int Immunol. 2016;28(2):87–97. doi: 10.1093/intimm/dxv053.
  25. Saiwai H, Kumamaru H, Ohkawa Y, et al. Ly6C+Ly6G– Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury. J Neurochem. 2013;125(1):74–88. doi: 10.1111/jnc.12135.
  26. Rodriguez PC, Augusto CO. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol 2008;222(1):180–91. doi: 10.1111/j.1600-065X.2008.00608.x.
  27. Srivastava MK, Sinha P, Clements VK, et al. Myeloid-derived suppressor cells inhibit T cell activation by depleting cystine and cysteine. Cancer Res. 2010;70(1):68–77. doi: 10.1158/0008-CAN-09-2587.
  28. Chevolet I, Speeckaert R, Schreuer M, et al. Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma. Oncoimmunology. 2015;4(3):e982382. doi: 10.4161/2162402X.2014.982382.
  29. Jitschin R, Braun M, Buttner M, et al. CLL-cells induce IDOhiCD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote Tregs. Blood. 2014;124(5):750–60. doi: 10.1182/blood-2013-12-
  30. Nagaraj S, Gupta K, Pisarev V, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 2007;13(7):828–35. doi: 10.1038/nm1609.
  31. Lu T, Ramakrishnan R, Altiok S, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin 2011;121(10):4015–4029. doi: 10.1172/JCI45862.
  32. Hanson EM, Clements VK, Sinha P, et al. Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J. Immunol. 2009;183(2):937–44. doi: 10.4049/jimmunol.0804253.
  33. Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1a, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–90. doi: 10.1084/jem.20131916.
  34. Filipazzi P, Valenti R, Huber V, et al. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007;25(18):2546–53. doi: 10.1200/JCO.2006.08.5829.
  35. Sinha P, Clements VK, Bunt SK, et al. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179(2):977–83. doi: 10.4049/jimmunol.179.2.977.
  36. Li H, Han Y, Guo Q, et al. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol. 2009;182(1):240–9. doi: 10.4049/jimmunol.182.1.240.
  37. Liu C, Yu S, Kappes J, et al. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood. 2007;109(10):4336–42. doi: 10.1182/blood-2006-09-
  38. Elkabets M, Ribeiro VSG, Dinarello CA, et al. IL-1b regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. Eur J Immunol. 2010;40(12):3347–57. doi: 10.1002/eji.201041037.
  39. Hoechst B, Voigtlaender T, Ormandy L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 2009;50(3):799–807. doi: 10.1002/hep.23054.
  40. Pan PY, Ma G, Weber KJ, et al. Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res. 2010;70(1):99–108. doi: 10.1158/0008-CAN-09-1882.
  41. Hoechst B, Gamrekelashvili J, Manns MP, et al. Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood. 2011;117(24):6532–41. doi: 10.1182/blood-2010-11-
  42. Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol. 2007;25(8):911–20. doi: 10.1038/nbt1323.
  43. Connolly MK, Mallen-St Clair J, Bedrosian AS, et al. Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leuk Biol. 2010;87(4):713–25. doi: 10.1189/jlb.0909607.
  44. Yang L, Huang J, Ren X, et al. Abrogation of TGFb signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell. 2008;13(1):23–35. doi: 10.1016/j.ccr.2007.12.004.
  45. Giles A, Vicioso Y, Kasai M, et al. Bone marrow-derived progenitor cells develop into myeloid-derived suppressor cells at metastatic sites. J Immunother Cancer. 2013;1(Suppl 1):188. doi: 10.1186/2051-1426-1-S1-P188.
  46. Solito S, Falisi E, Diaz-Montero CM, et al. A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood. 2011;118(8):2254–65. doi: 10.1182/blood-2010-12-
  47. Marigo I, Bosio E, Solito S, et al. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity. 2010;32(6):790–802. doi: 10.1016/j.immuni.2010.05.010.
  48. Highfill SL, Rodriguez PC, Zhou Q, et al. Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood. 2010;116(25):5738–47. doi: 10.1182/blood-2010-06-
  49. Lechner MG, Liebertz DJ, Epstein AL. Characterization of cytokine-induced myeloid derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol. 2010;185(4):2273–84. doi: 10.4049/jimmunol.1000901.
  50. Atretkhany KS, Nosenko MA, Gogoleva VS, et al. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation. Front Immunol. 2016;7:147. doi: 10.3389/fimmu.2016.00147.
  51. De Veirman K, Van Valckenborgh E, Lahmar Q, et al. Myeloid-derived suppressor cells as therapeutic target in hematological malignancies. Front Oncol. 2014;4:349. doi: 10.3389/fonc.2014.00349.
  52. Ramachandran I, Martner A, Pisklakova A, et al. Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol. 2013;190(7):3815–23. doi: 10.4049/jimmunol.1203373.
  53. De Veirman K, Van Ginderachter JA, Lub S, et al. Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells. Oncotarget. 2015;6(12):10532–47. doi: 10.18632/oncotarget.3300.
  54. Brimnes MK, Vangsted AJ, Knudsen LM, et al. Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol. 2010;72(6):540–7. doi: 10.1111/j.1365-2010.02463.x.
  55. Gorgun GT, Whitehill G, Anderson JL, et al. Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood. 2013;121(15):2975–87. doi: 10.1182/blood-2012-08-
  56. Gorgun GТ, Samur MK, Cowens KB, et al. Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma. Clin Cancer Res. 2015;21(20):4607–18. doi: 10.1158/1078-CCR-15-0200.
  57. Busch A, Zeh D, Janzen V, et al. Treatment with lenalidomide induces immuno-activating and counter-regulatory immunosuppressive changes in myeloma patients. Clin Exp Immunol. 2014;177(2):439–53. doi: 10.1111/cei.12343.
  58. Wang Z, Zhang L, Wang H, et al. Tumor-induced CD14+HLA-DR (-/low) myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients. Cancer Immunol Immunother. 2015;64(3):389–99. doi: 10.1007/s00262-014-1646-
  59. De Keersmaecker B, Fostier K, Corthals J, et al. Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation. Cancer Immunol Immunother. 2014;63(10):1023–36. doi: 10.1007/s00262-014-1571-
  60. Castella B, Foglietta M, Sciancalepore P, et al. Anergic bone marrow Vg9Vd2 T cells as early and long-lasting markers of PD-1-targetable microenvironment-induced immune suppression in human myeloma. Oncoimmunology. 2015;4(11):e1047580. doi: 10.1080/2162402X.2015.1047580.
  61. Giallongo C, Tibullo D, Parrinello NL, et al. Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC). Oncotarget. 2016;7(52):85764– doi: 10.18632/oncotarget.7969.
  62. Lee SE, Lim JY, Ryu DB, et al. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma. Cancer Immunol Immunother. 2016;65(8):983–94. doi: 10.1007/s00262-016-1861-
  63. Favaloro J, Liyadipitiya T, Brown R, et al. Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma. Leuk Lymphoma. 2014;55(12):2893–900. doi: 10.3109/10428194.2014.904511.
  64. Franssen LE, van de Donk NW, Emmelot ME, et al. The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. Bone Marrow Transplant. 2015;50(6):822–8. doi: 10.1038/bmt.2015.48.
  65. Lin Y, Gustafson MP, Bulur PA, et al. Immunosuppressive CD14+HLA-DRlow/– monocytes in B-cell non-Hodgkin lymphoma. Blood. 2011;117(3):872–81. doi: 10.1182/blood-2010-05-
  66. Tadmor T, Fell R, Polliack A, et al. Absolute monocytosis at diagnosis correlates with survival in diffuse large B-cell lymphoma—possible link with monocytic myeloid-derived suppressor cells. Hematol 2013;31(2):65–71. doi: 10.1002/hon.2019.
  67. Gustafson MP, Lin Y, LaPlant B, et al. Immune monitoring using the predictive power of immune profiles. J Immunother Cancer. 2013;1(1):7. doi: 10.1186/2051-1426-1-7.
  68. Wu C, Wu X, Zhang X, et al. Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large B-cell lymphoma. Int J Clin Exp Med. 2015;8(9):15173–81.
  69. Sato Y, Shimizu K, Shinga J, et al. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma. Oncoimmunology. 2015;4(3):e995541. doi: 10.1080/2162402X.2014.995541.
  70. Romano A, Parrinello NL, Vetro C, et al. Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy. Br J Haematol. 2015;168(5):689–700. doi: 10.1111/bjh.13198.
  71. Marini O, Spina C, Mimiola E, et al. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients. Oncotarget. 2016;19(7):27677–88. doi: 10.18632/oncotarget.8507.
  72. Azzaoui I, Uhel F, Rossille D, et al. T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12. Blood. 2016;128(8):1081–92. doi: 10.1182/blood-2015-08-
  73. Zhang H, Li ZL, Ye SB, et al. Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator. Cancer Immunol Immunother. 2015;64(12):1587- doi: 10.1007/s00262-015-1765-6.
  74. Christiansson L, Sоderlund S, Svensson E, et al. Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia. PLoS One. 2013;8(1):e55818. doi: 10.1371/journal.pone.0055818.
  75. Giallongo C, Romano A, Parrinello NL, et al. Mesenchymal Stem Cells (MSC) Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC) in Chronic Myeloid Leukemia Patients. PLoS One. 2016;11(7):e0158392. doi: 10.1371/journal.pone.0158392.
  76. Gustafson МP, Abraham RS, Lin Y, et al. Association of an increased frequency of CD14+HLA-DRlo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL). Br J Haematol. 2012;156(5):674–6. doi: 10.1111/j.1365-2011.08902.x.
  77. Liu J, Zhou Y, Huang Q, et al. CD14+HLA-DRlow/– expression: a novel prognostic factor in chronic lymphocytic leukemia. Oncol 2015;9(3):1167–72. doi: 10.3892/ol.2014.2808.
  78. Sun H, Li Y, Zhang ZF, et al. Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia. Int J Hematol. 2015;102(5):579–86. doi: 10.1007/s12185-015-1865-
  79. Gleason MK, Ross JA, Warlick ED, et al. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014;123(19):3016–26. doi: 10.1182/blood-2013-10-
  80. Chen X, Eksioglu EA, Zhou J, et al. Induction of myelodysplasia by myeloid-derived suppressor cells. J Clin Invest. 2013;123(11):4595–611. doi: 10.1172/JCI67580.
  81. Kittang AO, Kordasti S, Sand KE, et al. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. Oncoimmunology. 2015;5(2):e1062208. doi: 10.1080/2162402X.2015.1062208.
  82. Noonan KA, Ghosh N, Rudraraju L, et al. Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma. Cancer Immunol Res. 2014;2(8):725–31. doi: 10.1158/2326-CIR-13-0213.