EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review)

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

NN Mamaev, AI Shakirova, EV Morozova, TL Gindina

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: nikmamaev524@gmail.com

For citation: Mamaev NN, Shakirova AI, Morozova EV, Gindina TL. EVI1-Positive Leukemias and Myelodysplastic Syndromes: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2021;14(1):103–17. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-103-117

ABSTRACT

The present review provides the analysis of theoretical background and therapy of prognostically poorest EVI1-positive myeloid leukemias and myelodysplastic syndromes which is performed at the RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation. The focus is on the evidence of the dominating role of EVI1 gene in impaired epigenetic regulation of hematopoiesis and, thus, on the feasibility of allogeneic hematopoietic stem cell transplantation with hypomethylating agents and/or trans-retinoic acid used for these diseases treatment.

Keywords: EVI1, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, allo-HSCT, hypomethylating agents, trans-retinoic acid.

Received: September 12, 2020

Accepted: December 6, 2020

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Barjesteh van Waalwijk van Doorn-Khosrovani S. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood. 2002;101(3):837–45. doi: 10.1182/blood-2002-05-1459.
  2. Lugthart S, van Drunen E, van Norden Y, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood. 2008;111(8):4329–37. doi: 10.1182/blood-2007-10-119230.
  3. Groschel S, Lugthart S, Schlenk RF, et al. High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol. 2010;28(12):2101–7. doi: 10.1200/JCO.2009.26.0646.
  4. Paquette RL, Nicoll J, Chalukya M, et al. Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors. Cancer Genet. 2011;204(7):392–7. doi: 10.1016/j.cancergen.2011.06.002.
  5. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миелодиспластические синдромы с высокой экспрессией гена EVI1: теоретические и клинические аспекты. Клиническая онкогематология. 2012;5(4):361–4.
    [Mamaev NN, Gorbunova AV, Gindina TL, et al. Leukemias and myelodysplastic syndromes with high expression of EVI1 gene: theoretical and clinical aspects. Klinicheskaya onkogematologiya. 2012;5(4):361–4. (In Russ)]
  6. Rogers HJ, Vardiman JW, Anastasi J, et al. Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study. Haematologica. 2014;99(5):821–9. doi: 10.3324/haematol.2013.096420.
  7. Reiter E, Greinix H, Rabitsch W, et al. Low curative potential of bone marrow transplantation for highly aggressive acute myelogenous leukemia with inversion inv(3)(q21q26) or homologous translocation t(3;3)(q21;q26). Ann Hematol. 2000;79(7):374–7. doi: 10.1007/s002770000158.
  8. He X, Wang Q, Cen J, et al. Predictive value of high EVI1 expression in AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation in first CR. Bone Marrow Transplant. 2016;51(7):921–7. doi: 10.1038/bmt.2016.71.
  9. Gindina TL, Mamaev NN, Afanasyev BV. Chromosome abnormalities and hematopoietic stem cell transplantation in acute leukemias. In: ML Larramendy, S Soloneski (eds). Chromosomal abnormalities – A hallmark manifestation of genomic instability. IntechOpen; 2017. рр. 71– doi: 10.5772/67802.
  10. Halaburda K, Labopin M, Houhou M, et al. AlloHSCT for inv(3)(q21;q26)/t(3;3)(q21;q26) AML: a report from the acute leukemia working party of the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018;53(6):683–91. doi: 10.1038/s41409-018-0165-x.
  11. Martinelli G, Ottaviani E, Buonamici S, et al. Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica. 2003;88(11):1221–8.
  12. Poppe B, Dastugue N, Vandesompele J, et al. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements. Genes Chromos Cancer. 2006;45(4):349–56. doi: 10.1002/gcc.20295.
  13. De Braekeleer M, Le Bris MJ, De Braekeleer E, et al. 3q26/EVI1 rearrangements in myeloid hemopathies: a cytogenetic review. Fut Oncol. 2015;11(11):1675–86. doi: 10.2217/fon.15.64.
  14. Mamaev NN, Gindina TL, Morozova EV, et al. Primary myelodysplastic syndrome with two rare recurrent chromosome abnormalities [t(3q26/2;q22 and trisomy 13] associated with resistance to chemotherapy and hematopoietic stem cell transplantation. Cell Ther Transplant. 2018;7(2):64–9. doi: 10/18620/ctt-1866-8836-2018-7-2-64-69.
  15. Hodge JC, Bosler D, Rubinstein L, et al. Molecular and pathologic characterization of AML with double inv(3)(q21q26.2). Cancer Genet. 2019;230:28–36. doi: 10.1016/j.cancergen.2018.08.007.
  16. Testoni N, Borsaru G, Martinelli G, et al. 3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features. Haematologica. 1999;84(8):690–4.
  17. Russell M, List A, Greenberg P, et al. Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. Blood. 1994;84(4):1243–8. doi: 10.1182/blood.V84.4.1243.1243.
  18. Groschel S, Schlenk RF, Engelmann J, et al. Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol. 2013;31(1):95–103. doi: 10.1200/JCO.2011.41.5505.
  19. Ho PA, Alonzo TA, Gerbing RB, et al. High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children’s oncology group. Br J Haematol. 2013;162(5):670–7. doi: 10.1111/bjh.12444.
  20. Zhang Y, Owens K, Hatem L, et al. Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia. Blood. 2013;122(16):2888–92. doi: 10.1182/blood-2012-08-453662.
  21. Mucenski ML, Taylor BA, Ihle JN, et al. Identification of a common ecotropic viral integration site, Evi-1, in the DNA of AKXD murine myeloid tumors. Mol Cell Biol. 1988;8(1):301–8. doi: 10.1128/mcb.8.1.301.
  22. Goyama S, Kurokawa M. Pathogenetic significance of ecotropic viral integration site-1 in hematological malignancies. Cancer Sci. 2009;100(6):990–5. doi: 10.1111/j.1349-7006.2009.01152.x.
  23. Hinai AA, Valk PJ. Review: Aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2016;172(6):870–8. doi: 10.1111/bjh.13898.
  24. Yuan X, Wang X, Bi K, Jiang G. The role of EVI-1 in normal hematopoiesis and myeloid malignancies (Review). Int J Oncol. 2015;47(6):2028–36. doi: 10.3892/ijo.2015.3207.
  25. Delwel R, Funabiki T, Kreider BL, et al. Four of the seven zinc fingers of the Evi-1 myeloid-transforming gene are required for sequence-specific binding to GA(C/T)AAGA(T/C)AAGATAA. Mol Cell Biol. 1993;13(7):4291–300. doi: 10.1128/mcb.13.7.4291.
  26. Funabiki T, Kreider BL, Ihle JN. The carboxyl domain of zinc fingers of the Evi-1 myeloid transforming gene binds a consensus sequence of GAAGATGAG. Oncogene. 1994;9(6):1575–81.
  27. Morishita K, Suzukawa K, Taki T, et al. EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC. Oncogene. 1995;10(10):1961–7.
  28. Perkins AS, Kim JH. Zinc fingers 1–7 of EVI1 fail to bind to the GATA motif by itself but require the core site GACAAGATA for binding. J Biol Chem. 1996;271(2):1104–10. doi: 10.1074/jbc.271.2.1104.
  29. Bartholomew C, Kilbey A, Clark AM, Walker M. The Evi-1 proto-oncogene encodes a transcriptional repressor activity associated with transformation. Oncogene. 1997;14(5):569–77. doi: 10.1038/sj.onc.1200864.
  30. Kilbey A, Bartholomew C. Evi-1 ZF1 DNA binding activity and a second distinct transcriptional repressor region are both required for optimal transformation of Rat1 fibroblasts. Oncogene. 1998;16(17):2287–91. doi: 10.1038/sj.onc.1201732.
  31. Bordereaux D, Fichelson S, Tambourin P, Gisselbrecht S. Alternative splicing of the Evi-1 zinc finger gene generates mRNAs which differ by the number of zinc finger motifs. Oncogene. 1990;5(6):925–7.
  32. Alzuherri H, McGilvray R, Kilbey A, Bartholomew C. Conservation and expression of a novel alternatively spliced Evi1 exon. Gene. 2006;384:154–62. doi: 10.1016/j.gene.2006.07.027.
  33. Fears S, Mathieu C, Zeleznik-Le N, et al. Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well as in myeloid leukemia and produces a new member of the PR domain family. Proc Natl Acad Sci USA. 1996;93(4):1642–7. doi: 10.1073/pnas.93.4.1642.
  34. Huang S, Shao G, Liu L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem. 1998;273(26):15933–9. doi: 10.1074/jbc.273.26.15933.
  35. Goyama S, Yamamoto G, Shimabe M, et al. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell. 2008;3(2):207–20. doi: 10.1016/j.stem.2008.06.002.
  36. Laricchia-Robbio L, Nucifora G. Significant increase of self-renewal in hematopoietic cells after forced expression of EVI1. Blood Cells Mol Dis. 2008;40(2):141–7. doi: 10.1016/j.bcmd.2007.07.012.
  37. Yoshimi A, Kurokawa M. Evi1 forms a bridge between the epigenetic machinery and signaling pathways. Oncotarget. 2011;2(7):575–86. doi: 10.18632/oncotarget.304.
  38. Buonamici S, Li D, Chi Y, et al. EVI1 induces myelodysplastic syndrome in mice. J Clin Invest. 2005;115(8):2296. doi: 1172/jci21716c1.
  39. Cuenco GM, Ren R. Both AML1 and EVI1 oncogenic components are required for the cooperation of AML1/MDS1/EVI1 with BCR/ABL in the induction of acute myelogenous leukemia in mice. Oncogene. 2004;23(2):569–79. doi: 10.1038/sj.onc.1207143.
  40. Glass C, Wilson M, Gonzalez R, et al. The role of EVI1 in myeloid malignancies. Blood Cells Mol Dis. 2014;53(1–2):67–76. doi: 10.1016/j.bcmd.2014.01.002.
  41. Jin G, Yamazaki Y, Takuwa M, et al. Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis. Blood. 2007;109(9):3998–4005. doi: 10.1182/blood-2006-08-041202.
  42. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818–22. doi: 10.1038/nature04980.
  43. Bindels EM, Havermans M, Lugthart S, et al. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs. Blood. 2012;119(24):5838–49. doi: 10.1182/blood-2011-11-393827.
  44. Glass C, Wuertzer C, Cui X, et al. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia. PLoS One. 2013;8(6):e67134. doi: 10.1371/journal.pone.0067134.
  45. Hoyt PR, Bartholomew C, Davis AJ, et al. The Evi1 proto-oncogene is required at midgestation for neural, heart, and paraxial mesenchyme development. Mech Dev. 1997;65(1–2):55–70. doi: 10.1016/s0925-4773(97)00057-9.
  46. Nucifora G. The EVI1 gene in myeloid leukemia. Leukemia. 1997;11(12):2022–31. doi: 10.1038/sj.leu.2400880.
  47. Kataoka K, Sato T, Yoshimi A, et al. Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med. 2011;208(12):2403–16. doi: 10.1084/jem.20110447.
  48. Zhang Y, Stehling-Sun S, Lezon-Geyda K, et al. PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function. Blood. 2011;118(14):3853–61. doi: 10.1182/blood-2011-02-334680.
  49. Steinleitner K, Rampetsreiter P, Koffel R, et al. EVI1 and MDS1/EVI1 expression during primary human hematopoietic progenitor cell differentiation into various myeloid lineages. Anticancer Res. 2012;32(11):4883–9.
  50. Wieser R. The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions. Gene. 2007;396(2):346–57. doi: 10.1016/j.gene.2007.04.012.
  51. Xi ZF, Russell M, Woodward S, et al. Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia. Leukemia. 1997;11(2):212–20. doi: 10.1038/sj.leu.2400547.
  52. Aytekin M, Vinatzer U, Musteanu M, et al. Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 5’-ends. Gene. 2005;356:160–8. doi: 10.1016/j.gene.2005.04.032.
  53. Niederreither K, Subbarayan Y, Dolle P, et al. Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nat Genet. 1999;21(4):444–8. doi: 1038/7788.
  54. Valk PJ, Verhaak RG, Beijen MA, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350(16):1617–28. doi: 10.1056/NEJMoa040465.
  55. Morishita K, Parganas E, William CL, et al. Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300–400 kilobases on chromosome band 3q26. Proc Natl Acad Sci USA. 1992;89(9):3937–41. doi: 10.1073/pnas.89.9.3937.
  56. Ogawa S, Mitani K, Kurokawa M, et al. Abnormal expression of Evi-1 gene in human leukemias. Hum Cell. 1996;9(4):323–32.
  57. Lugthart S, Groschel S, Beverloo HB, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol. 2010;28(24):3890–8. doi: 10.1200/JCO.2010.29.2771.
  58. Groschel S, Sanders MA, Hoogenboezem R, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125(1):133–9. doi: 10.1182/blood-2014-07-591461.
  59. Langabeer SE, Rogers JR, Harrison G, et al. EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2001;112(1):208–11. doi: 10.1046/j.1365-2141.2001.02569.x.
  60. Balgobind BV, Lugthart S, Hollink IH, et al. EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia. Leukemia. 2010;24(5):942–9. doi: 10.1038/leu.2010.47.
  61. Matsuo H, Kajihara M, Tomizawa D, et al. EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia. Haematologica. 2014;99(11):e225–е227. doi: 10.3324/haematol.2014.107128.
  62. Testa U, Lo-Coco F. Targeting of leukemia-initiating cells in acute promyelocytic leukemia. Stem Cell Invest. 2015;2:8. doi: 10.3978/j.issn.2306-9759.2015.04.03.
  63. Jo A, Mitani S, Shiba N, et al. High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML. Leukemia. 2015;29(5):1076–83. doi: 10.1038/leu.2015.5.
  64. Sadeghian MH, Rezaei Dezaki Z. Prognostic Value of EVI1 Expression in Pediatric Acute Myeloid Leukemia: A Systematic Review. Iran J Pathol. 2018;13(3):294–300.
  65. Arai S, Yoshimi A, Shimabe M, et al. Evi-1 is a transcriptional target of mixed-lineage leukemia oncoproteins in hematopoietic stem cells. Blood. 2011;117(23):6304–14. doi: 10.1182/blood-2009-07-234310.
  66. De Weer A, Van der Meulen J, Rondou P, et al. EVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells. Br J Haematol. 2011;154(3):337–48. doi: 10.1111/j.1365-2141.2011.08737.x.
  67. 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.
  68. Groschel S, Sanders MA, Hoogenboezem R, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157(2):369–81. doi: 10.1016/j.cell.2014.02.019.
  69. Lugthart S, Figueroa ME, Bindels E, et al. Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1. Blood. 2011;117(1):234–41. doi: 10.1182/blood-2010-04-281337.
  70. Bartholomew C, Morishita K, Askew D, et al. Retroviral insertions in the CB-1/Fim-3 common site of integration activate expression of the Evi-1 gene. Oncogene. 1989;4(5):529–34.
  71. Kreider BL, Orkin SH, Ihle JN. Loss of erythropoietin responsiveness in erythroid progenitors due to expression of the Evi-1 myeloid-transforming gene. Proc Natl Acad Sci USA. 1993;90(14):6454–8. doi: 10.1073/pnas.90.14.6454.
  72. Kataoka K, Kurokawa M. Ecotropic viral integration site 1, stem cell self-renewal and leukemogenesis. Cancer Sci. 2012;103(8):1371–7. doi: 10.1111/j.1349-7006.2012.02303.x.
  73. Soderholm J, Kobayashi H, Mathieu C, et al. The leukemia-associated gene MDS1/EVI1 is a new type of GATA-binding transactivator. Leukemia. 1997;11(3):352–8. doi: 10.1038/sj.leu.2400584.
  74. Laricchia-Robbio L, Fazzina R, Li D, et al. Point mutations in two EVI1 Zn fingers abolish EVI1-GATA1 interaction and allow erythroid differentiation of murine bone marrow cells. Mol Cell Biol. 2006;26(20):7658–66. doi: 10.1128/MCB.00363-06.
  75. Senyuk V, Sinha KK, Li D, et al. Repression of RUNX1 activity by EVI1: a new role of EVI1 in leukemogenesis. Cancer Res. 2007;67(12):5658–66. doi: 10.1158/0008-5472.CAN-06-3962.
  76. Laricchia-Robbio L, Premanand K, Rinaldi CR, Nucifora G. EVI1 Impairs myelopoiesis by deregulation of PU.1 function. Cancer Res. 2009;69(4):1633–42. doi: 10.1158/0008-5472.CAN-08-2562.
  77. Steinmetz B, Hackl H, Slabakova E, et al. The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid. Cell Cycle. 2014;13(18):2931–43. doi: 10.4161/15384101.2014.946869.
  78. Yuasa H, Oike Y, Iwama A, et al. Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO J. 2005;24(11):1976–87. doi: 10.1038/sj.emboj.7600679.
  79. Shimabe M, Goyama S, Watanabe-Okochi N, et al. Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene. 2009;28(49):4364–74. doi: 10.1038/onc.2009.288.
  80. Kurokawa M, Mitani K, Irie K, et al. The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3. Nature. 1998;394(6688):92–6. doi: 10.1038/27945.
  81. Izutsu K, Kurokawa M, Imai Y, et al. The corepressor CtBP interacts with Evi-1 to repress transforming growth factor beta signaling. Blood. 2001;97(9):2815–22. doi: 10.1182/blood.v97.9.2815.
  82. Kurokawa M, Mitani K, Yamagata T, et al. The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J. 2000;19(12):2958–68. doi: 10.1093/emboj/19.12.2958.
  83. Buonamici S, Li D, Mikhail FM, et al. EVI1 abrogates interferon-alpha response by selectively blocking PML induction. J Biol Chem. 2004;280(1):428–36. doi: 10.1074/jbc.M410836200.
  84. Pradhan AK, Mohapatra AD, Nayak KB, Chakraborty S. Acetylation of the proto-oncogene EVI1 abrogates Bcl-xL promoter binding and induces apoptosis. PLoS One. 2011;6(9):e25370. doi: 10.1371/journal.pone.0025370.
  85. Yatsula B, Lin S, Read AJ, et al. Identification of binding sites of EVI1 in mammalian cells. J Biol Chem. 2005;280(35):30712–22. doi: 10.1074/jbc.M504293200.
  86. Ernst T, Chase AJ, Score J, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42(8):722–6. doi: 10.1038/ng.621.
  87. Figueroa ME, Lugthart S, Li Y, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 2010;17(1):13–27. doi: 10.1016/j.ccr.2009.11.020.
  88. Wagner JM, Hackanson B, Lubbert M, Jung M. Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy. Clin Epigenet. 2010;1(3–4):117–36. doi: 10.1007/s13148-010-0012-4.
  89. Senyuk V, Zhang Y, Liu Y, et al. Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis. Proc Natl Acad Sci USA. 2013;110(14):5594–9. doi: 10.1073/pnas.1302645110.
  90. Nikoloski G, Langemeijer SM, Kuiper RP, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 2010;42(8):665–7. doi: 10.1038/ng.620.
  91. Makishima H, Jankowska AM, Tiu RV, et al. Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies. Leukemia. 2010;24(10):1799–804. doi: 10.1038/leu.2010.167.
  92. 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.
  93. Walter MJ, Ding L, Shen D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia. 2011;25(7):1153–8. doi: 10.1038/leu.2011.44.
  94. 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.
  95. 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.
  96. 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.
  97. van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41(5):521–3. doi: 10.1038/ng.349.
  98. Liu Y, Chen L, Ko TC, et al. Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT. Oncogene. 2006;25(25):3565–75. doi: 10.1038/sj.onc.1209403.
  99. Yoshimi A, Goyama S, Watanabe-Okochi N, et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood. 2011;117(13):3617–28. doi: 10.1182/blood-2009-12-261602.
  100. Bingemann SC, Konrad TA, Wieser R. Zinc finger transcription factor ecotropic viral integration site 1 is induced by all-trans retinoic acid (ATRA) and acts as a dual modulator of the ATRA response. FEBS J. 2009;276(22):6810–22. doi: 10.1111/j.1742-4658.2009.07398.x.
  101. Pauebelle E, Plesa A, Hayette S, et al. Efficacy of All-Trans-Retinoic Acid in high-risk acute myeloid leukemia with overexpression of EVI1. Oncol Ther. 2019;7(2):121–30. doi: 10.1007/s40487-019-0095-9.
  102. Vazquez I, Maicas M, Cervera J, et al. Down-regulation of EVI1 is associated with epigenetic alterations and good prognosis in patients with acute myeloid leukemia. Haematologica. 2011;96(10):1448–56. doi: 10.3324/haematol.2011. 040535.
  103. Daghistani M, Marin D, Khorashad JS, et al. EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors. Blood. 2010;116(26):6014–7. doi: 10.1182/blood-2010-01-264234.
  104. Мамаев Н.Н., Шакирова А.И., Бархатов И.М. идр. Ведущая роль BAALC-экспрессирующих клеток-предшественниц в возникновении и развитии посттрансплантационных рецидивов у больных острыми миелоидными лейкозами. Клиническая онкогематология. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88.
    [Mamaev NN, Shakirova AI, Barkhatov IM, et al. Crucial Role of BAALC–Expressing Progenitor Cells in Emergence and Development of Post-Transplantation Relapses in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2020;13(1):75–88. doi: 10.21320/2500-2139-2020-13-1-75-88. (In Russ)]
  105. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8. doi: 10.1038/367645a0.
  106. Matsushita H, Yahata T, Sheng Y, et al. Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice. PLoS One. 2014;9(11):e111082. doi: 10.1371/journal.pone.0111082.
  107. Cole CB, Verdoni AM, Ketkar S, et al. PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia. J Clin Invest. 2016;126(1):85–98. doi: 10.1172/JCI82897.
  108. Гудожникова Я.В., Мамаев Н.Н., Бархатов И.М. и др. Результаты молекулярного мониторинга в посттрансплантационный период с помощью серийного исследования уровня экспрессии гена WT1 у больных острыми миелоидными лейкозами. Клиническая онкогематология. 2018;11(3):241–51. doi: 10.21320/2500-2139-2018-11-3-241-251.
    [Gudozhnikova YaV, Mamaev NN, Barkhatov IM, et al. Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia. Clinical oncohematology. 2018;11(3):241–51. doi: 10.21320/2500-2139-2018-11-3-241-251. (In Russ)]
  109. Dreyfus F, Bouscary D, Melle J, et al. Expression of the Evi-1 gene in myelodysplastic syndromes. Leukemia. 1995;9(1):203–5. doi: 10.1016/0145-2126(94)90237-2.
  110. Thol F, Yun H, Sonntag AK, et al. Prognostic significance of combined MN1, ERG, BAALC, and EVI1 (MEBE) expression in patients with myelodysplastic syndromes. Ann Hematol. 2012;91(8):1221–33. doi: 10.1007/s00277-012-1457-7.
  111. Russell M, Thompson F, Spier C, Taetle R. Expression of the EVI1 gene in chronic myelogenous leukemia in blast crisis. Leukemia. 1993;7(10):1654–7.
  112. Ogawa S, Kurokawa M, Tanaka T, et al. Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia. Leukemia. 1996;10(5):788–94.
  113. Kuila N, Sahoo DP, Kumari M, et al. EVI1, BAALC and AME: prevalence of the secondary mutations in chronic and accelerated phases of chronic myeloid leukemia patients from eastern India. Leuk Res. 2009;33(4):594–6. doi: 10.1016/j.leukres.2008.07.018.
  114. Горбунова А.В., Гиндина Т.Л., Морозова Е.В. и др. Влияние молекулярно-генетических и цитогенетических факторов на эффективность аллогенной трансплантации костного мозга у больных хроническим миелолейкозом. Клиническая онкогематология. 2013;6(4):445–50.
    [Gorbunova AV, Gindina TL, Morozova EV, et al. Impact of molecular genetic and cytogenetic characteristics on outcomes of allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia. Klinicheskaya oncogematologiya. 2013;6(4):445–50. (In Russ)]
  115. Sato T, Goyama S, Kataoka K, et al. Evi1 defines leukemia-initiating capacity and tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Oncogene. 2014;33(42):5028–38. doi: 10.1038/onc.2014.108.
  116. Konantz M, Andre MC, Ebinger M, et al. EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia. Leukemia. 2013;27(1):56–65. doi: 10.1038/leu.2012.211.
  117. Mittal N, Li L, Sheng Y, et al. A critical role of epigenetic inactivation of miR-9 in EVI1high pediatric AML. Mol Cancer. 2019;18(1):30. doi: 10.1186/s12943-019-0952-z.
  118. Verhagen HJ, Smit MA, Rutten A, et al. Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid. Blood. 2016;127(4):458–63. doi: 10.1182/blood-2015-07-653840.
  119. Мамаев Н.Н, Горбунова А.В, Гиндина Т.Л. и др. Стойкое восстановление донорского гемопоэза у больной с посттрансплантационным рецидивом острого миеломонобластного лейкоза с inv(3)(q21q26), моносомией 7 и экспрессией онкогена EVI1 после трансфузий донорских лимфоцитов и использования гипометилирующих агентов. Клиническая онкогематология. 2014;7(1):71–5.
    [Mamayev NN, Gorbunova AV, Gindina TL, et al. Stable donor hematopoiesis reconstitution after post­transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), –7 and EVI1 oncogene overexpression treated by donor lymphocyte infusions and hypomethylating agents. Klinicheskaya oncogematologiya. 2014;7(1):71–5. (In Russ)]
  120. He X, Wang Q, Cen J, et al. Predictive value of high EVI1 expression in AML patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation in first CR. Bone Marrow Transplant. 2016;51(7):921–7. doi: 10.1038/bmt.2016.71.
  121. Мамаев Н.Н., Морозова Е.В., Горбунова А.В. Теоретические и клинические аспекты эпигенетических изменений при миелодиспластических синдромах и острых нелимфобластных лейкозах (обзор литературы). Вестник гематологии. 2011;7(3):12–21.
    [Mamaev NN, Morozova EV, Gorbunova AV. Theoretical and practical aspects of epigenetic changes in myelodysplastic syndromes and acute non-lymphoblastic leukemias (literature review). Vestnik gematologii. 2011;7(3):12–21. (In Russ)]
  122. Mamaev N, Morozova E, Gindina T, et al. Dacogen and allogeneic bone marrow transplantation in the treatment of high-risk myelodysplastic syndromes with non-random chromosome abnormalities. Leuk Res. 2011;35(Suppl 1):72–3. doi: 10.1016/S0145-2126(11)70186-2.
  123. Mamaev N, Gorbunova A, Barkhatov I, et al. Biology and treatment of leukemia and myelodysplastic syndromes with high EVI-1 gene expression. ELN Frontiers Meeting 2012 “Myeloid neoplasms: approaching cure”. Istanbul, Turkey. Abstract No. 37.
  124. Yang X, Wong MPM, Ng RK. Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications. Int J Mol Sci. 2019;20(18):4576. doi: 10.3390/ijms20184576.
  125. Nowek K, Sun SM, Dijkstra MK, et al. Expression of a passenger miR-9* predicts favorable outcome in adults with acute myeloid leukemia less than 60 years of age. Leukemia. 2016;30(2):303–9. doi: 10.1038/leu.2015.282.
  126. Li F, He W, Geng R, Xie X. Myeloid leukemia with high EVI1 expression is sensitive to 5-aza-2’-deoxycytidine by targeting miR-9. Clin Transl Oncol. 2020;22(1):137–43. doi: 10.1007/s12094-019-02121-y.
  127. Cattaneo F, Nucifora G. EVI1 recruits the histone methyltransferase SUV39H1 for transcription repression. J Cell Biochem. 2008;105(2):344–52. doi: 10.1002/jcb.21869.
  128. Craddock C, Quek L, Goardon N, et al. Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia. 2013;27(5):1028–36. doi: 10.1038/leu.2012.312.
  129. Trino S, Zoppoli P, Carella AM, et al. DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation. Stem Cell Res Ther. 2019;10(1):138. doi: 10.1186/s13287-019-1245-6.
  130. Ahn JS, Kim YK, Min YH, et al. Azacitidine Pre-Treatment Followed by Reduced-Intensity Stem Cell Transplantation in Patients with Higher-Risk Myelodysplastic Syndrome. Acta Haematol. 2015;134(1):40–8. doi: 10.1159/000368711.
  131. Voso MT, Leone G, Piciocchi A, et al. Feasibility of allogeneic stem-cell transplantation after azacitidine bridge in higher-risk myelodysplastic syndromes and low blast count acute myeloid leukemia: results of the BMT-AZA prospective study. Ann Oncol. 2017;28(7):1547–53. doi: 10.1093/annonc/mdx154.
  132. Овечкина В.Н., Бондаренко С.Н., Морозова Е.В. и др. Роль терапии гипометилирующими препаратами перед аллогенной трансплантацией гемопоэтических стволовых клеток при острых миелоидных лейкозах и миелодиспластическом синдроме. Клиническая онкогематология. 2017;10(3):351–7. doi: 10.21320/2500-2139-2017-10-3-351-357.
    [Ovechkina VN, Bondarenko SN, Morozova EV, et al. The Role of Hypomethylating Agents Prior to Allogeneic Hematopoietic Stem Cells Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2017;10(3):351–7. doi: 10.21320/2500-2139-2017-10-3-351-357. (In Russ)]
  133. Nishihori T, Perkins J, Mishra A, et al. Pretransplantation 5-azacitidine in high-risk myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014;20(6):776–80. doi: 10.1016/j.bbmt.2014.02.008.
  134. de Lima M, Giralt S, Thall PF, et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 2010;116(23):5420–31. doi: 10.1002/cncr.25500.
  135. Craddock C, Jilani N, Siddique S, et al. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial. Biol Blood Marrow Transplant. 2016;22(2):385–90. doi: 10.1016/j.bbmt.2015.09.004.
  136. Marini C, Brissot E, Bazarbachi A, et al. Tolerability and Efficacy of Treatment With Azacytidine as Prophylactic or Preemptive Therapy for Myeloid Neoplasms After Allogeneic Stem Cell Transplantation. Clin Lymphoma Myel Leuk. 2020;20(6):377–82. doi: 10.1016/j.clml.2019.10.011.
  137. Бадаев Р.Ш., Заммоева Д.Б., Гиршова Л.Л. и др. Профилактическое применение азацитидина у пациентов с острыми миелоидными лейкозами после гаплоидентичной аллоТКМ. Клиническая онкогематология. 2019;12(1):37–42. doi: 10.21320/2500-2139-2019-12-1-37-42.
    [Badaev RSh, Zammoeva DB, Girshova LL, et al. Preventive Use of Azacitidine in Patients with Acute Myeloid Leukemia after Haploidentical Allo-BMT. Clinical oncohematology. 2019;12(1):37–42. doi: 10.21320/2500-2139-2019-12-1-37-42. (In Russ)]
  138. Cattaneo F, Nucifora G. EVI1 recruits the histone methyltransferase SUV39H1 for transcription repression. J Cell Biochem. 2008;105(2):344–52. doi: 10.1002/jcb.21869.
  139. Estey EH, Thall PF, Pierce S, et al. Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin ± all-trans retinoic acid ± granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Blood. 1999;93(8):2478–84. doi: 10.1182/blood.v93.8.2478.
  140. Schlenk RF, Frohling S, Hartmann F, et al. Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia. 2004;18(11):1798–803. doi: 10.1038/sj.leu.2403528.
  141. Raza A, Buonamici S, Lisak L, et al. Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression. Leuk Res. 2004;28(8):791–803. doi: 10.1016/j.leukres.2003.11.018.
  142. Burnett AK, Hills RK, Green C, et al. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA. Blood. 2010;115(5):948–56. doi: 10.1182/blood-2009-08-236588.
  143. van Gils N, Verhagen HJMP, Smit L. Reprogramming acute myeloid leukemia into sensitivity for retinoic-acid-driven differentiation. Exp Hematol. 2017;52:12–23. doi: 10.1016/j.exphem.2017.04.007.
  144. Plesa A, Dumontet C, Mattei E, et al. High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia. World J Stem Cells. 2017;9(12):227–34. doi: 10.4252/wjsc.v9.i12.227.
  145. Nguyen CH, Bauer K, Hackl H, et al. All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia. Cell Death Dis. 2019;10(12):944. doi: 10.1038/s41419-019-2172-2.
  146. Field T, Perkins J, Huang Y, et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010;45(2):255–60. doi: 10.1038/bmt.2009.134.
  147. Kim DY, Lee JH, Park YH, et al. Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant. 2012;47(3):374–9. doi: 10.1038/bmt.2011.86.
  148. Jiang YZ, Su GP, Dai Y, et al. Effect of Decitabine Combined with Unrelated Cord Blood Transplantation in an Adult Patient with -7/EVI1+ Acute Myeloid Leukemia: a Case Report and Literature Review. Ann Clin Lab Sci. 2015;45(5):598–601.
  149. Schlenk RF, Lubbert M, Benner A, et al. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Ann Hematol. 2016;95(12):1931–42. doi: 10.1007/s00277-016-2810-z.
  150. Taussig DC, Vargaftig J, Miraki-Moud F, et al. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction. Blood. 2010;115(10):1976–84. doi: 10.1182/blood-2009-02-206565.
  151. Patel S, Zhang Y, Cassinat B, et al. Successful xenografts of AML3 samples in immunodeficient NOD/shi-SCID IL2Rγ–/– Leukemia. 2012;26(11):2432–5. doi: 10.1038/leu.2012.154.