Association between HLA-DRB1 alleles and response to imatinib in chronic myeloid leukemia

E.G. Ovsyannikova1, I.L. Davydkin2, E.A. Popov1, L.V. Zaklyakova1, and B.N. Levitan1

1 Astrakhan State Medical Academy, RF Ministry of Health, Astrakhan, Russian Federation

2 Research Institute of Hematology, Transfusiology, and Intensive Care, Samara State Medical University, RF Ministry of Health, Samara, Russian Federation


ABSTRACT

The article presents analysis of association between the HLA-DRB1 gene alleles and the response to imatinib in the patients with Ph-positive chronic myeloid leukemia (Ph+ CML). HLA class II alleles, DRB1 locus, were determined using PCR-SSP. The predictors of optimal response to imatinib in 3 to 18-months treatment of CML are HLA-DRB1*16(02), HLA-DRB1*17(03), and HLA-DRB1*08 specificities. Immunogenetic markers of imatinib treatment failure are HLA-DRB1*11(05), HLA-DRB1*12(05), and HLA-DRB1*14(06) alleles. The results obtained can be used for the development of individual long-term prognosis for chronic myeloid leukemia and optimization of the treatment choice.


Keywords: chronic myeloid leukemia, HLA-DRB1, imatinib, prognosis.

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REFERENCES

  1. Deininger M., O’Brien S.G., Guilhot F. et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood 2009; 114: 1126 (abstr.).
  2. Apperley J.F. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007; 8: 1018–29.
  3. Soverini S., Hochhaus A. et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood 2011; 18(5): 1208–15.
  4. Li L., Wang L., Li L. et al. Activation of p53 by SIRT1 Inhibition Enhances Elimination of CML Leukemia Stem Cells in Combination with Imatinib. Cancer Cell 2012; 21: 266–81.
  5. Ferrandiz N., Caraballoa J. M., Albajara M. et al. p21(Cip1) confers resistance to imatinib in human chronic myeloid leukaemia с Cancer Lett. 2010; 292(1): 133–9.
  6. Guillem V., Amat P., Cervantes F. et al. Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia. Res. 2012; 36(2): 174–81.
  7. Marin D., Gabriel I.H., Ahmad S. et al. KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly diagnosed chronic myeloid leukemia patients treated with imatinib. Leukemia 2012; 26(2): 296–302.
  8. Хаитов P.M., Дедов И.И., Болдырева М.Н. Новые представления о функции главного комплекса генов иммунного ответа человека. Мол. мед. 2006; 3: 47–51. [Khaitov P.M., Dedov I.I., Boldyreva M.N. Novye predstavleniya o funktsii glavnogo kompleksa genov immunnogo otveta cheloveka (New concepts of function of human major immune response gene complex. In: Mol. med.). Mol. med. 2006; 3: 47–51.]
  9. Короткова И.Ю. Клиническая иммуногенетика заболеваний, злокачественных новообразований и хронических воспалительных процессов: Дис. ¼ д-ра мед. наук. Новосибирск, 2007. [Korotkova I.Yu. Klinicheskaya immunogenetika zabolevaniy, zlokachestvennykh novoobrazovaniy i khronicheskikh vospalitelnykh protsessov: Dis. ¼ d-ra med. nauk (Clinical immunogenetics of diseases, malignancies, and chronic inflammatory processes. Dissertation for the degree of DSci). Novosibirsk, 2007.]
  10. Соколова Ю.В. Роль полиморфизма генов иммуноглобулинподобных рецепторов киллерных клеток, их лигандов и генов HLA в патогенезе и прогнозе множественной миеломы: Автореф. дис. ¼ канд. биол. наук. СПб., 2012. [Sokolova Yu.V. Rol polimorfizma genov immunoglobulinpodobnykh retseptorov killernykh kletok, ikh ligandov i genov HLA v patogeneze i prognoze mnozhestvennoy miyelomy: Avtoref. dis. ¼ kand. biol. nauk (Role of Ig-like killer cell receptor gene polymorphism, their ligands, and HLA genes in pathogenesis and prognosis of multiple myeloma. Author’s summary of dissertation for the degree of PhD). Spb., 2012.]
  11. Villalobos C., Rivera S., Weir-Medina J. et al. Association of HLA class I and leukemia in mestizo patients of the state of Zulia, Venezuela. Clin. 2003; 44(4): 283–9.
  12. Wei L., Xiao L., Wu X.Y. et al. Expression and analysis of HLA-A, B and DRB1 genes in patients with chronic myelogenous leukemia in Guangdong area. Journal of experimental hematology. Chinese Assoc. Pathophysiol. 2008; 16(4): 915–8.
  13. Naugler C., Liwski R. HLA risk markers for chronic myelogenous leukemia in Eastern Canada. Lymphoma 2009; 50(2): 254–9.
  14. Хамаганова Е.Г. Активная вакцинация при хроническом миелолейкозе. Гематол. и трансфузиол. 2008; 53(2): 42–8. [Khamaganova Ye.G. Aktivnaya vaktsinatsiya pri khronicheskom miyeloleykoze [Active immunization in chronic myelogenous leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2008; 53(2): 42–8.]
  15. Mannering S.I., Mckenzie J.L, Feamley D.В., Hart D.N.J. HLA-DRlrestricted bcr-abl (b3a2)-specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3а2 peptide and antigen presenting cells exposed to b3a2- containing cell lysates. Blood 1997; 90: 290–7.
  16. Хамаганова Е.Г., Зарецкая Ю.М. Молекулярные механизмы ассоциаций HLA-системы с резистентностью к развитию хронического миелолейкоза. Гематол. и трансфузиол. 2006; 1: 12–7. [Khamaganova Ye.G., Zaretskaya YU.M. Molekulyarnye mekhanizmy assotsiatsiy HLA-sistemy s rezistentnostyu k razvitiyu khronicheskogo miyeloleykoza (Molecular mechanisms of associations between HLA system and resistance to development of chronic myelogenous leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2006; 1: 12–7.]
  17. Bosch ten G.J., Kessler J.H., Joosten A.C. et al. A BCR-ABL oncoprotein p210 b2а2 fusion region sequence is recognized by HLA-DR2a-restricted cytotoxic T lymphocytes and presented by HLA-DR-matched cells transfected with an L-li (b2а2) construct. Blood 1999; 94: 1038–45.
  18. Максимов О.Д., Зайцев Г.А., Бутина Е.В. Распределение HLA-маркеров при хроническом лимфолейкозе. Гематол. и трансфузиол. 2003; 1: 19–22. Maksimov O.D., (Zaytsev G.A., Butina Ye.V. Raspredeleniye HLA-markerov pri khronicheskom limfoleykoze [HLA markers distribution in chronic lymphocytic leukemia. In: Hematol. & transfuziol.). Gematol. i transfuziol. 2003; 1: 19–22.]
  19. Сенькина Е.А. Клиническое значение полиморфизма HLA- специфичностей классов I, II и иммунных нарушений при множественной миеломе: Автореф. дис. ¼ канд. мед. наук. СПб., 2010. [Senkina Ye.A. Klinicheskoye znacheniye polimorfizma HLA-spetsifichnostey klassov I, II i immunnykh narusheniy pri mnozhestvennoy miyelome: Avtoref. dis. ¼ kand. med. nauk (Clinical significance of HLA class I and class II specificity polymorphism and immunological disorders in multiple myeloma]. Author’s summary of dissertation for the degree of PHD). SPb., 2010.]
  20. Shi J., Tricot G.J., Garg T.K. et al. Bortezomib down-regulates the cell surface expression of HLA-class I and enhances natural killer cell-mediated lysis of myeloma. Blood 2008; 111(3): 1309–17.
  21. Овсянникова Е.Г., Исрапилова З.М., Заклякова Л.В. Анализ распре- деления аллелей гена HLA-DRB1 у больных хроническим миелолейкозом. Науч. ведомости Белгородского гос. ун-та. 2011; 22 (117): 110–4. [Ovsyannikova Ye.G., Israpilova Z.M., Zaklyakova L.V. Analiz raspredeleniya alleley gena HLA-DRB1 u bolnykh khronicheskim miyeloleykozom (Analysis of HLA DRB1 allele distribution in patients with chronic myelogenous leukemia. In: Scientif. bulletin of Belgorod St. Univers.). Nauch. vedomosti Belgorodskogo gos. un-ta. 2011; 22 (117): 110–4.]
  22. Овсянникова Е.Г., Исрапилова З.М., Заклякова Л.В., Попов Е.А. Аллельный полиморфизм гена HLA-DRB1 при хроническом миелолейкозе. Фундамент. исслед. 2011; 10(3): 538–54. [Ovsyannikova Ye.G., Israpilova Z.M., Zaklyakova L.V., Popov Ye.A. Allelnyy polimorfizm gena HLA-DRB1 pri khronicheskom miyeloleykoze (HLA DRB1 allele polymorphism in chronic myelogenous leukemia. In: Fundament. stud.). Fundament. issled. 2011; 10(3): 538–54.]
  23. Baccarani M., Cortes J., Pane F. et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. Clin. Oncol. 2009; 27(35): 6041–51.
  24. Сароянц Л.В., Болдырева М.Н., Гуськова И.А. и др. Иммуногенетические маркеры предрасположенности к лепре у русских жителей Астрахан- ского региона. Иммунология 2005; 5: 263–7. [Saroyants L.V., Boldyreva M.N., Guskova I.A. i dr. Immunogeneticheskiye markery predraspolozhennosti k lepre u russkikh zhiteley Astrakhanskogo regiona (Immunogenetic markers of susceptibility to leprosy in Russian population of Astrakhan’ region. In: Immunology). Immunologiya 2005; 5: 263–7.]