Molecular Monitoring of RUNX1-RUNX1T1 Transcript Level in Acute Myeloblastic Leukemias on Treatment

L.L. Girshova, Ekaterina Gennad’evna Ovsyannikova, S.O. Kuzin, E.N. Goryunova, R.I. Vabishchevich, A.V. Petrov, D.V. Motorin, D.V. Babenetskaya, V.V. Ivanov, K.V. Bogdanov, I.V. Kholopova, T.S. Nikulina, Yu.V. Mirolyubova, Yu.A. Alekseeva, A.Yu. Zaritskii,

DOI:

https://doi.org/10.21320/2500-2139-2016-9-4-456-464

Background. The current approach to treatment of acute myeloblastic leukemia (AML) includes the achievement of maximum tumor reduction and, therefore, eradication of a leukemic clone. The goal of the therapy is to achieve undetectable levels of the target gene, except an isolated molecular rearrangement of RUNX1-RUNX1T1.

Aim. To estimate the dynamics of the RUNX1-RUNX1T1 level and relevant clinical manifestations during the monitoring of various stages of the program therapy and after its completion.

Methods. The article presents a description of 10 cases of AML with isolated RUNX1-RUNX1T1 expression (n = 4) and the expression in combination with different molecular and cytogenetic abnormalities (= 6). In addition, a long-term monitoring of the gene expression by quantitative determination of RUNX1-RUNX1T1 using a real-time PCR was presented.

Results. The incidence of relapses in a group with a decreased RUNX1-RUNX1T1 expression level of >2 log is 75 % as compared to patients with a less significant reduction of the transcript level (with the relapse incidence equal to 0 %) (= 0.05). The increase of the RUNX1-RUNX1T1 level against the background of bone marrow remission by more than 1 log coincided with a bone marrow relapse within 5–18 weeks. In addition, long-term persistence of a certain transcript level after the completion of a program therapy without relapse is possible.

Conclusion. The study analyzed possible molecular background of different clinical outcomes of long-term persistence of the RUNX1-RUNX1T1 transcript that might lead to an individualized approach to AML patients.

  • L.L. Girshova VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • Ekaterina Gennad’evna Ovsyannikova VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • S.O. Kuzin VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • E.N. Goryunova VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • R.I. Vabishchevich VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • A.V. Petrov VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • D.V. Motorin VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • D.V. Babenetskaya VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • V.V. Ivanov VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • K.V. Bogdanov VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • I.V. Kholopova VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • T.S. Nikulina VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • Yu.V. Mirolyubova VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • Yu.A. Alekseeva VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  • A.Yu. Zaritskii VA Almazov Federal North-West Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341 ; ФГБУ «Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России, ул. Аккуратова, д. 2, Санкт-Петербург, Российская Федерация, 197341
  1. Bitter MA, Le Beau MM, Rowley JD, et al. Association between morphology, karyotype, and clinical features in myeloid leukemias. Hum Pathol. 1987;18(3):211–25. doi: 10.1016/s0046-8177(87)80002-3. DOI: https://doi.org/10.1016/S0046-8177(87)80002-3
  2. Mrozek K, Heinonen K, de la Chapelle A, Bloomfield CD. Clinical significance of cytogenetics in acute myeloid leukemia. Semin Oncol. 1997;24(1):17–31.
  3. Rowe D, Cotterill SJ, Ross FM, et al. Cytogenetically cryptic AML1-ETO and CBFbeta-MYH11 gene rearrangement: incidence in 412 cases of acute myeloid leukaemia. Br J Haematol. 2000;111(4):1051–6. doi: 10.1111/j.1365-2141.2000.02474.x. DOI: https://doi.org/10.1046/j.1365-2141.2000.02474.x
  4. Downing JR. AML1/CBFbeta transcription complex: its role in normal hematopoiesis and leukemia. Leukemia. 2001;15(4):664–5. doi: 10.1038/sj.leu.2402035. DOI: https://doi.org/10.1038/sj.leu.2402035
  5. Рулина А.В., Спирин П.В., Прасолов В.С. Активированные лейкозные онкогены AML1-ETO и C-KIT: роль в развитии острого миелоидного лейкоза и современные подходы к их ингибированию. Успехи биологической химии. 2010;50:349–86.
  6. [Rulina AV, Spirin PV, Prasolov VS. Activated leukemic AML1-ETO и C-KIT oncogenes: their role in the development of acute myeloid leukemia and modern approaches to their inhibition. Uspekhi biologicheskoi khimii. 2010;50:349–86. (In Russ)]
  7. Grimwade D, Walker H, Oliver F, et al. A on behalf of the Medical Research Council Adult and Children’s Leukaemia Working Parties. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. Blood. 1998;92(7):2322–33. DOI: https://doi.org/10.1182/blood.V92.7.2322
  8. Lowenberg B. Postremission treatment of acute myelogenous leukemia. N Eng J Med. 1995;332(4):260–2. doi: 10.1056/nejm199501263320411. DOI: https://doi.org/10.1056/NEJM199501263320411
  9. Byrd JC, Dodge RK, Carroll A, et al. Patients with t(8;21) (q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered. J Clin Oncol. 1999;17(12):3767–75. DOI: https://doi.org/10.1200/JCO.1999.17.12.3767
  10. Byrd JC, Mrozek K, Dodge RK, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood. 2002;100(13):4325–36. doi: 10.1182/blood-2002-03-0772. DOI: https://doi.org/10.1182/blood-2002-03-0772
  11. Byrd JC, Ruppert AS, Mrozek K, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16) (p13q22) or t(16;16): results from CALGB 8461. J Clin Oncol. 2004;22(6):1087–94. doi: 10.1200/jco.2004.07.012. DOI: https://doi.org/10.1200/JCO.2004.07.012
  12. Schlenk RF, Benner A, Krauter J, et al. Individual patient data-based meta-analysis of patients aged 16 to 60 years with core binding factor acute myeloid leukemia: a survey of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol. 2004;22(18):3741–50. doi: 10.1200/jco.2004.03.012. DOI: https://doi.org/10.1200/JCO.2004.03.012
  13. Marcucci G, Mrozek K, Ruppert AS, et al. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B Study. J Clin Oncol. 2005;23(24):5705–17. doi: 10.1200/jco.2005.15.610. DOI: https://doi.org/10.1200/JCO.2005.15.610
  14. Yin JAL, O’Brien MA, Hills RK, et al. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: Results of the United Kingdom MRC AML-15 Trial. Blood. 2012;120(14):2826–35. doi: 10.1182/blood-2012-06-435669. DOI: https://doi.org/10.1182/blood-2012-06-435669
  15. Jourdan E, Boissel N, Chevret S, et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013;121(12):2213–23. doi: 10.1182/blood-2012-10-462879. DOI: https://doi.org/10.1182/blood-2012-10-462879
  16. Byrd JC, Weiss RB, Arthur DC, et al. Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol. 1997;15(2):466–75. DOI: https://doi.org/10.1200/JCO.1997.15.2.466
  17. Nguyen S, Leblanc T, Fenaux P, et al. A white blood cell index as the main prognostic factor in t(8;21) acute myeloid leukemia (AML): a survey of 161 cases from the French AML Intergroup. Blood. 2002;99(10):3517–23. doi: 10.1182/blood.V99.10.3517. DOI: https://doi.org/10.1182/blood.V99.10.3517
  18. Baer MR, Stewart CC, Lawrence D, et al. Expression of the neural cell adhesion molecule CD56 is associated with short remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22). Blood. 1997;90(4):1643–8. DOI: https://doi.org/10.1182/blood.V90.4.1643.1643_1643_1648
  19. Schoch C, Haase D, Haferlach T, et al. Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Leukemia. 1996;10(8):1288–95.
  20. 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. DOI: https://doi.org/10.1200/JCO.2006.06.9500
  21. 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. DOI: https://doi.org/10.1038/sj.leu.2404188
  22. Hoyos M, Nomdedeu JF, Esteve J, et al. Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease. Eur J Haematol. 2013;91(3):209–18. doi: 10.1111/ejh.12130. DOI: https://doi.org/10.1111/ejh.12130
  23. Демидова И.А. Использование молекулярно-биологических методов для определения генетических нарушений при миелоидных лейкозах и мониторирования минимальной остаточной болезни. Онкогематология. 2007;4:17–25.
  24. [Demidova IA. Application of molecular-biological methods for determining genetic disorders in myeloid leukemias and monitoring of minimal residual diseases. Onkogematologiya. 2007;4:17–25. (In Russ)]
  25. Estey EH. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol. 2013;88(4):318–27. doi: 10.1002/ajh.23404. DOI: https://doi.org/10.1002/ajh.23404
  26. Buccisano F, Maurillo L, Del Principe MI, et al. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood. 2012;119(2):332–41. doi: 10.1182/blood-2011-08-363291. DOI: https://doi.org/10.1182/blood-2011-08-363291
  27. Tobal K, Newton J, Nige S, et al. Molecular quantitation of minimal residual disease in acute myeloid leukemia with с t(8;21) can identify patients in durable remission and predict clinical relapse. Blood. 2000;95(3):815–9. DOI: https://doi.org/10.1182/blood.V95.3.815.003k30_815_819
  28. Yin JAL, O’Brien MA, Hills RK, et al. Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: Results of the United Kingdom MRC AML-15 Trial. Blood. 2012;120(14):2826–30. doi: 10.1182/blood-2012-06-435669. DOI: https://doi.org/10.1182/blood-2012-06-435669
  29. Jourdan E, Boissel N, Chevret S, et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood. 2013;121(12):2213–23. doi: 10.1182/blood-2012-10-462879. DOI: https://doi.org/10.1182/blood-2012-10-462879
  30. Zhu H-H, Zhang X-H, Qin Y-Z, et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood. 2013;121(2):4056–62. doi: 10.1182/blood-2012-11-468348. DOI: https://doi.org/10.1182/blood-2012-11-468348
  31. Morschhauser F, Cayuela JM, Martini S, et al. Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients. J Clin Oncol. 2000;18(4):778–94. DOI: https://doi.org/10.1200/JCO.2000.18.4.788
  32. Willekens C, Blanchet O, Renneville A, et al. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial. Haematologica. 2016;101(3):328–35. doi: 10.3324/haematol.2015.131946. DOI: https://doi.org/10.3324/haematol.2015.131946
  33. Schnittger S, Weisser M, Schoch C, et al. New score predicting for prognosis in PML-RARA+, AML1-ETO+, or CBFBMYH11+ acute myeloid leukemia based on quantification of fusion transcripts. Blood. 2003;102(8):2746–55. doi: 10.1182/blood-2003-03-0880. DOI: https://doi.org/10.1182/blood-2003-03-0880
  34. Ommen HB, Schnittger S, Jovanovic JV, et al. Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias. Blood. 2010;115(2):198–205. doi: 10.1182/blood-2009-04-212530. DOI: https://doi.org/10.1182/blood-2009-04-212530
  35. Krauter J, Gorlich K, Ottmann O, et al. Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias. J Clin Oncol. 2003;21(23):4413–22. doi: 10.1200/jco.2003.03.166. DOI: https://doi.org/10.1200/JCO.2003.03.166
  36. Marcucci G, Livak KJ, Bi W, et al. Detection of minimal residual disease in patients with AML1/ETO-associated acute myeloid leukemia using a novel quantitative reverse ttranscriptase polymerase chain reaction assay. Leukemia. 1998;12(9):1482–9. doi: 10.1038/sj.leu.2401128. DOI: https://doi.org/10.1038/sj.leu.2401128
  37. Lane S, Saal R, Molle P, et al. A ³ 1 log rise in RQ-PCR transcript levels defines molecular relapse in core binding factor acute myeloid leukemia and predicts subsequent morphologic relapse. Leuk Lymphoma. 2008;49(3):517–23. doi: 10.1080/10428190701817266. DOI: https://doi.org/10.1080/10428190701817266
  38. Perrea G, Lasa A, Aventi A, et al. Prognostic value of minimal residual disease in acute myeloid leukemia with favorable cytogenetics [t(8.21) and inv(16)]. Leukemia. 2006;20(1):87–94. doi: 10.1038/sj.leu.2404015. DOI: https://doi.org/10.1038/sj.leu.2404015
  39. Jaso JM, Wang SA, Jorgensen JL, et al. Multicolor flow cytometric immunophenotyping for detection of minimal residual disease in AML: Past, present and future. Bone Marrow Transplant. 2014;49(9):1129–38. doi: 10.1038/bmt.2014.99. DOI: https://doi.org/10.1038/bmt.2014.99
  40. Bruggermann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107(3):1116–23. doi: 10.1182/blood-2005-07-2708. DOI: https://doi.org/10.1182/blood-2005-07-2708
  41. Borowitz MJ, Devidas M, Hunger SP, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship in other prognostic factors: a Children’s Oncology Group Study. Blood. 2008;111(12):5477–85. doi: 10.1182/blood-2008-01-132837. DOI: https://doi.org/10.1182/blood-2008-01-132837
  42. Muller MC, Cross NC, Erben P, et al. Harmonisation of molecular monitoring of CML therapy in Europe. Leukemia. 2009;23(11):1957–63. doi: 10.1038/leu.2009.168. DOI: https://doi.org/10.1038/leu.2009.168
  43. Jurlander J, Caligiuri MA, Ruutu T, et al. Persistence of the AMLI/ETO Fusion Transcript in Patients Treated With Allogeneic Bone Marrow Transplantation for t(8;21) Leukemia. Blood. 1996;88(6):2183–219. DOI: https://doi.org/10.1182/blood.V88.6.2183.bloodjournal8862183
  44. Kayser S, Schlenk RF, Grimwade D, et al. Minimal residual disease–directed therapy in acute myeloid leukemia. Blood. 2015;125(15):2331–5. doi: 10.1182/blood-2014-11-578815. DOI: https://doi.org/10.1182/blood-2014-11-578815
  45. Evans PA, Short MA, Jack AS, et al. Detection and quantitation of the transcripts associated with the inv(16) in presentation and follow-up samples from patients with AML. Leukemia. 1997;11(3):364–9. doi: 10.1038/sj.leu.2400578. DOI: https://doi.org/10.1038/sj.leu.2400578
  46. Laczika K, Novak M, Hilgarth B, et al. Competitive CBFbeta/MYH11 reverse transcriptase polymerase chain reaction for quantitative assessment of minimal residual disease during post remission therapy in acute myeloid leukemia with inversion 16: a pilot study. J Clin Oncol. 1998;16(4):1519–25. DOI: https://doi.org/10.1200/JCO.1998.16.4.1519
  47. Krauter J, Hoellge W, Wattjies MP, et al. Detection and quantitation of CBFB/MYH11 fusion transcript in patients with inv(16) positive acute myeloblastic leukemia by real-time RT-PCR. Genes Chromos Cancer. 2001;30(4):342–8. doi: 10.1002/gcc.1100. DOI: https://doi.org/10.1002/gcc.1100
  48. Marcucci G, Caligiuri MA, Dohner H, et al. Quantification of CBFbeta/MYH11 fusion trancript byreal-time RT-PCR in patients with inv(16) acute myeloid leukemia. Leukemia. 2001;15(7):1072–80. doi: 10.1038/sj.leu.2402159. DOI: https://doi.org/10.1038/sj.leu.2402159
  49. Duployez N, Willekens C, Marceau-Renaut A, et al. Prognosis and monitoring of core-binding factor acute myeloid leukemia: current and emerging factors. Exp Rev Hematol. 2014;8(1):43–56. doi: 10.1586/17474086.2014.976551. DOI: https://doi.org/10.1586/17474086.2014.976551
  50. Shima T, Miyamoto T, Kikushige Y, et al. The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. Exp Hematol. 2014;42(11):955–65. doi: 10.1016/j.exphem.2014.07.267. DOI: https://doi.org/10.1016/j.exphem.2014.07.267
  51. Buonamici S, Ottaviani E, Visani G, et al. Patterns of AML-ETO1 transcript expression in patients with acute myeloid leukemia and t(8;21) in complete hematologic remission. Haematologica. 2004;89(1):103–5.
  52. Song J, Mercer D, Hu X, et al. Common Leukemia- and Lymphoma-Associated Genetic Aberrations in Healthy Individuals. J Mol Diagn. 2011;13(2);213–9. doi: 10.1016/j.jmoldx.2010.10.009. DOI: https://doi.org/10.1016/j.jmoldx.2010.10.009
  53. Miyamoto T, Weissman IL, Akashi K. AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Nat Acad Sci. 2000;97(13):7521–6. doi: 10.1073/pnas.97.13.7521. DOI: https://doi.org/10.1073/pnas.97.13.7521
  54. Yin JAL, Tobal K. Detection of minimal residual disease in acute myeloid leukemias: methodologies, clinical and biological significance. Br J Haematol. 1999;106(3):578–90. doi: 10.1046/j.1365-2141.1999.01522.x. DOI: https://doi.org/10.1046/j.1365-2141.1999.01522.x
  55. Corces-Zimmerman MR, Hong W-J, Weissman IL, et al. Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Nat Acad Sci. 2014;111(7):2548–53. doi: 10.1073/pnas.1324297111. DOI: https://doi.org/10.1073/pnas.1324297111
  56. Russler-Germain DA, Spencer DH, Young MA, et al. The R882H DNMT3A Mutation Associated with AML Dominantly Inhibits Wild-Type DNMT3A by Blocking Its Ability to Form Active Tetramers. Cancer Cell. 2014;25(4):442–54. doi: 10.1016/j.ccr.2014.02.010. DOI: https://doi.org/10.1016/j.ccr.2014.02.010
  57. Ommen HB, Schnittger S, Jovanovic JV, et al. Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias. Blood. 2010;115(2):198–205. doi: 10.1182/blood-2009-04-212530. DOI: https://doi.org/10.1182/blood-2009-04-212530
  58. Wang Y, Wu D-P, Liu Q-F, et al. In adults with t(8;21) AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood. 2014;124(12):1880–6. doi: 10.1182/blood-2014-03-563403. DOI: https://doi.org/10.1182/blood-2014-03-563403

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Published

01.10.2016

Issue

MYELOID TUMORS

How to Cite

Girshova L.L., Ovsyannikova E.G., Kuzin S.O., et al. Molecular Monitoring of RUNX1-RUNX1T1 Transcript Level in Acute Myeloblastic Leukemias on Treatment. Clinical Oncohematology. Basic Research and Clinical Practice. 2016;9(4):456–464. doi:10.21320/2500-2139-2016-9-4-456-464.

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