Epigenetic deregulation in myeloid malignancies

Translational Research

Volumn 165, Issue 1, 2015, Pages 102-114

  Meldi, Kristen M ^a   Figueroa, Maria E ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE INHIBITOR; HISTONE; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; TEN ELEVEN TRANSLOCATION PROTEIN; UNCLASSIFIED DRUG; DNA METHYLTRANSFERASE; ENZYME INHIBITOR;

ACUTE GRANULOCYTIC LEUKEMIA; CELL DIFFERENTIATION; DNA METHYLATION; DNA MODIFICATION; DRUG DESIGN; EPIGENETICS; GENE EXPRESSION PROFILING; GENE TARGETING; GENE TRANSLOCATION; GENETIC REGULATION; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMOGENESIS; MIXED LINEAGE LEUKEMIA TRANSLOCATION; MODIFIER GENE; MUTATION; MYELODYSPLASTIC SYNDROME; REVIEW; SOMATIC MUTATION; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; LEUKEMIA, MYELOID, ACUTE; METABOLISM; MYELODYSPLASTIC SYNDROMES; TRANSLATIONAL RESEARCH;

ANIMALS; DNA METHYLATION; DNA MODIFICATION METHYLASES; ENZYME INHIBITORS; EPIGENESIS, GENETIC; HISTONES; HUMANS; LEUKEMIA, MYELOID, ACUTE; MUTATION; MYELODYSPLASTIC SYNDROMES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84919844806     PISSN: 19315244     EISSN: 18781810     Source Type: Journal    
DOI: 10.1016/j.trsl.2014.04.012     Document Type: Review

References (125)

1. O. Abdel-Wahab, A. Mullally, and C. Hedvat Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies Blood 114 2009 144 147
2. T.J. Ley, L. Ding, and M.J. Walter DNMT3A mutations in acute myeloid leukemia N Engl J Med 363 2010 2424 2433
3. J.P. Patel, M. Gonen, and M.E. Figueroa Prognostic relevance of integrated genetic profiling in acute myeloid leukemia N Engl J Med 366 2012 1079 1089
4. A. Portela, and M. Esteller Epigenetic modifications and human disease Nat Biotechnol 28 2010 1057 1068
5. S.B. Baylin, and P.A. Jones A decade of exploring the cancer epigenome - biological and translational implications Nat Rev Cancer 11 2011 726 734
6. M.V. Gomes, and G.G. Pelosi Epigenetic vulnerability and the environmental influence on health Exp Biol Med 238 2013 859 865
7. Y. Yamashita, J. Yuan, and I. Suetake Array-based genomic resequencing of human leukemia Oncogene 29 2010 3723 3731
8. M.J. Walter, L. Ding, and D. Shen Recurrent DNMT3A mutations in patients with myelodysplastic syndromes Leukemia 25 2011 1153 1158
9. A.F. Ribeiro, M. Pratcorona, and C. Erpelinck-Verschueren Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia Blood 119 2012 5824 5831
10. S.J. Kim, H. Zhao, S. Hardikar, A.K. Singh, M.A. Goodell, and T. Chen A DNMT3A mutation common in AML exhibits dominant-negative effects in murine ES cells Blood 122 2013 4086 4089
11. D.A. Russler-Germain, D.H. Spencer, and M.A. Young The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers Cancer Cell 25 2014 442 454
12. F. Thol, C. Winschel, and A. Ludeking Rare occurrence of DNMT3A mutations in myelodysplastic syndromes Haematologica 96 2011 1870 1873
13. G.A. Challen, D. Sun, and M. Jeong Dnmt3a is essential for hematopoietic stem cell differentiation Nat Genet 44 2012 23 31
14. C.B. Cole, J.M. Klco, and T.J. Ley DNMT3A R882H overexpression leads to hematopoietic and skin alterations in transgenic mice Blood 122 2013 479
15. J. Xu, Y.Y. Wang, and Y.J. Dai DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells Proc Natl Acad Sci U S A 111 2014 2620 2625
16. L.I. Shlush, S. Zandi, and A. Mitchell Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia Nature 506 2014 328 333
17. M. Tahiliani, K.P. Koh, and Y. Shen Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 Science 324 2009 930 935
18. Y.F. He, B.Z. Li, and Z. Li Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA Science 333 2011 1303 1307
19. H. Wu, A.C. D'Alessio, and S. Ito Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells Genes Dev 25 2011 679 684
20. C.G. Lian, Y. Xu, and C. Ceol Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma Cell 150 2012 1135 1146
21. O. Kosmider, V. Gelsi-Boyer, and M. Ciudad TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia Haematologica 94 2009 1676 1681
22. F. Delhommeau, S. Dupont, and V. Della Valle Mutation in TET2 in myeloid cancers N Engl J Med 360 2009 2289 2301
23. A. Tefferi, K.H. Lim, and O. Abdel-Wahab Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML Leukemia 23 2009 1343 1345
24. K. Moran-Crusio, L. Reavie, and A. Shih Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation Cancer Cell 20 2011 11 24
25. C. Quivoron, L. Couronne, and V. Della Valle TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis Cancer Cell 20 2011 25 38
26. M. Ko, H.S. Bandukwala, and J. An Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice Proc Natl Acad Sci U S A 108 2011 14566 14571
27. Z. Li, X. Cai, and C.L. Cai Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies Blood 118 2011 4509 4518
28. M. Ko, Y. Huang, and A.M. Jankowska Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2 Nature 468 2010 839 843
29. J. Yamazaki, R. Taby, and A. Vasanthakumar Effects of TET2 mutations on DNA methylation in chronic myelomonocytic leukemia Epigenetics 7 2012 201 207
30. M.E. Figueroa, O. Abdel-Wahab, and C. Lu Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation Cancer Cell 18 2010 553 567
31. W. Xu, H. Yang, and Y. Liu Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases Cancer Cell 19 2011 17 30
32. L. Dang, D.W. White, and S. Gross Cancer-associated IDH1 mutations produce 2-hydroxyglutarate Nature 465 2010 966
33. P.S. Ward, J. Patel, and D.R. Wise The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate Cancer Cell 17 2010 225 234
34. C. Lu, P.S. Ward, and G.S. Kapoor IDH mutation impairs histone demethylation and results in a block to cell differentiation Nature 483 2012 474 478
35. M. Sasaki, C.B. Knobbe, and J.C. Munger IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics Nature 488 2012 656 659
36. M. Xiao, H. Yang, and W. Xu Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors Genes Dev 26 2012 1326 1338
37. E. Letouze, C. Martinelli, and C. Loriot SDH mutations establish a hypermethylator phenotype in paraganglioma Cancer Cell 23 2013 739 752
38. E.F. Mason, and J.L. Hornick Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine production in gastrointestinal stromal tumors: implications for mechanisms of tumorigenesis Mod Pathol 26 2013 1492 1497
39. L.J. Castro-Vega, A. Buffet, and A.A. De Cubas Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas Hum Mol Genet 23 2014 2440 2446
40. M. Jeong, D. Sun, and M. Luo Large conserved domains of low DNA methylation maintained by Dnmt3a Nat Genet 46 2014 17 23
41. M.C. Cox, P. Panetta, and F. Lo-Coco Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: results in 378 adult patients Am J Clin Pathol 122 2004 298 306
42. P.H. Sorensen, C.S. Chen, and F.O. Smith Molecular rearrangements of the MLL gene are present in most cases of infant acute myeloid leukemia and are strongly correlated with monocytic or myelomonocytic phenotypes J Clin Invest 93 1994 429 437
43. T. Muto, G. Sashida, and M. Oshima Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders J Exp Med 210 2013 2627 2639
44. S.N. Khan, A.M. Jankowska, and R. Mahfouz Multiple mechanisms deregulate EZH2 and histone H3 lysine 27 epigenetic changes in myeloid malignancies Leukemia 27 2013 1301 1309
45. T. Ernst, A.J. Chase, and J. Score Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders Nat Genet 42 2010 722 726
46. G. Nikoloski, S.M. Langemeijer, and R.P. Kuiper Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes Nat Gene 42 2010 665 667
47. H. Makishima, A.M. Jankowska, and R.V. Tiu Novel homo- and hemizygous mutations in EZH2 in myeloid malignancies Leukemia 24 2010 1799 1804
48. R. Bejar, K.E. Stevenson, and B.A. Caughey Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes J Clin Oncol 30 2012 3376 3382
49. J. Wang, X. Ai, and R.P. Gale TET2, ASXL1 and EZH2 mutations in Chinese with myelodysplastic syndromes Leuk Res 37 2013 305 311
50. R. Bejar, K. Stevenson, and O. Abdel-Wahab Clinical effect of point mutations in myelodysplastic syndromes N Engl J Med 364 2011 2496 2506
51. R.D. Morin, N.A. Johnson, and T.M. Severson Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin Nat Genet 42 2010 181 185
52. E. Vire, C. Brenner, and R. Deplus The Polycomb group protein EZH2 directly controls DNA methylation Nature 439 2006 871 874
53. J. Yu, J. Yu, and D.R. Rhodes A polycomb repression signature in metastatic prostate cancer predicts cancer outcome Cancer Res 67 2007 10657 10663
54. V. Gelsi-Boyer, V. Trouplin, and J. Adelaide Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia Br J Haematol 145 2009 788 800
55. O. Abdel-Wahab, J. Patel, and R.L. Levine Clinical implications of novel mutations in epigenetic modifiers in AML Hematol Oncol Clin North Am 25 2011 1119 1133
56. O. Abdel-Wahab, M. Adli, and L.M. LaFave ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression Cancer Cell 22 2012 180 193
57. O. Abdel-Wahab, J. Gao, and M. Adli Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo J Exp Med 210 2013 2641 2659
58. J. Son, S.S. Shen, R. Margueron, and D. Reinberg Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin Genes Dev 27 2013 2663 2677
59. A. Puda, J.D. Milosevic, and T. Berg Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies Am J Hematol 87 2012 245 250
60. J. Score, C. Hidalgo-Curtis, and A.V. Jones Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms Blood 119 2012 1208 1213
61. S. Hong, Y.W. Cho, L.R. Yu, H. Yu, T.D. Veenstra, and K. Ge Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases Proc Natl Acad Sci U S A 104 2007 18439 18444
62. K. Agger, P.A. Cloos, and J. Christensen UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development Nature 449 2007 731 734
63. M.G. Lee, R. Villa, and P. Trojer Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination Science 318 2007 447 450
64. A.M. Jankowska, H. Makishima, and R.V. Tiu Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A Blood 118 2011 3932 3941
65. G. van Haaften, G.L. Dalgliesh, and H. Davies Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer Nat Genet 41 2009 521 523
66. S.Y. Jo, E.M. Granowicz, I. Maillard, D. Thomas, and J.L. Hess Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation Blood 117 2011 4759 4768
67. K.M. Bernt, N. Zhu, and A.U. Sinha MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L Cancer Cell 20 2011 66 78
68. A.T. Nguyen, O. Taranova, J. He, and Y. Zhang DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis Blood 117 2011 6912 6922
69. M.J. Chang, H. Wu, and N.J. Achille Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes Cancer Res 70 2010 10234 10242
70. M.E. Figueroa, S. Lugthart, and Y. Li DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia Cancer Cell 17 2010 13 27
71. L. Bullinger, M. Ehrich, and K. Dohner Quantitative DNA methylation predicts survival in adult acute myeloid leukemia Blood 115 2010 636 642
72. M.E. Figueroa, L. Skrabanek, and Y. Li MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation Blood 114 2009 3448 3458
73. A. Akalin, F.E. Garrett-Bakelman, and M. Kormaksson Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia PLoS Genet 8 2012 e1002781
74. A.M. Broske, L. Vockentanz, and S. Kharazi DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction Nat Genet 41 2009 1207 1215
75. J.J. Trowbridge, A.U. Sinha, N. Zhu, M. Li, S.A. Armstrong, and S.H. Orkin Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains Genes Dev 26 2012 344 349
76. C.A. Eads, A.E. Nickel, and P.W. Laird Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice Cancer Res 62 2002 1296 1299
77. B.N. Trinh, T.I. Long, A.E. Nickel, D. Shibata, and P.W. Laird DNA methyltransferase deficiency modifies cancer susceptibility in mice lacking DNA mismatch repair Mol Cell Biol 22 2002 2906 2917
78. M.E. Figueroa, S.C. Chen, and A.K. Andersson Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia J Clin Invest 123 2013 3099 3111
79. K. Ghoshal, J. Datta, and S. Majumder 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal Mol Cell Biol 25 2005 4727 4741
80. K. Patel, J. Dickson, S. Din, K. Macleod, D. Jodrell, and B. Ramsahoye Targeting of 5-aza-2'-deoxycytidine residues by chromatin-associated DNMT1 induces proteasomal degradation of the free enzyme Nucleic Acids Res 38 2010 4313 4324
81. S.S. Palii, B.O. Van Emburgh, U.T. Sankpal, K.D. Brown, and K.D. Robertson DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B Mol Cell Biol 28 2008 752 771
82. A. Cihak, J.W. Weiss, and H.C. Pitot Effects of 5-azacytidine on hepatic polyribosomes and maturation of ribosomal RNA Acta Biol Med Ger 33 1974 859 865
83. M. Reichman, and S. Penman The mechanism of inhibition of protein synthesis by 5-azacytidine in HeLa cells Biochim Biophys Acta 324 1973 282 289
84. L.W. Lu, G.H. Chiang, D. Medina, and K. Randerath Drug effects on nucleic acid modification. I. A specific effect of 5-azacytidine on mammalian transfer RNA methylation in vivo Biochem Biophys Res Commun 68 1976 1094 1101
85. P.W. Hollenbach, A.N. Nguyen, and H. Brady A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines PLoS One 5 2010 e9001
86. E.A. Griffiths, and S.D. Gore DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes Semin Hematol 45 2008 23 30
87. Y.F. Wong, L.M. Jakt, and S. Nishikawa Prolonged treatment with DNMT inhibitors induces distinct effects in promoters and gene-bodies PLoS One 8 2013 e71099
88. T.E. Fandy, J.G. Herman, and P. Kerns Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies Blood 114 2009 2764 2773
89. R. Itzykson, O. Kosmider, and T. Cluzeau Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias Leukemia 25 2011 1147 1152
90. F. Traina, V. Visconte, and P. Elson Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms Leukemia 28 2014 78 87
91. L. Shen, H. Kantarjian, and Y. Guo DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes J Clin Oncol 28 2010 605 613
92. M. Nakagawa, Y. Oda, and T. Eguchi Expression profile of class I histone deacetylases in human cancer tissues Oncol Rep 18 2007 769 774
93. G. Garcia-Manero, H. Yang, and C. Bueso-Ramos Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes Blood 111 2008 1060 1066
94. G. Garcia-Manero, S. Assouline, and J. Cortes Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia Blood 112 2008 981 989
95. F. Giles, T. Fischer, and J. Cortes A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies Clin Cancer Res 12 2006 4628 4635
96. I. Gojo, A. Jiemjit, and J.B. Trepel Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias Blood 109 2007 2781 2790
97. A. Quintas-Cardama, F.P. Santos, and G. Garcia-Manero Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia Leukemia 25 2011 226 235
98. A.O. Soriano, H. Yang, and S. Faderl Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome Blood 110 2007 2302 2308
99. G. Garcia-Manero, H.M. Kantarjian, and B. Sanchez-Gonzalez Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia Blood 108 2006 3271 3279
100. Y. Hu, W. Lu, and G. Chen Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound beta-phenylethyl isothiocyanate Blood 116 2010 2732 2741
101. W. Fiskus, Y. Wang, and A. Sreekumar Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells Blood 114 2009 2733 2743
102. H. Yang, K. Hoshino, B. Sanchez-Gonzalez, H. Kantarjian, and G. Garcia-Manero Antileukemia activity of the combination of 5-aza-2'-deoxycytidine with valproic acid Leuk Res 29 2005 739 748
103. E.E. Cameron, K.E. Bachman, S. Myohanen, J.G. Herman, and S.B. Baylin Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer Nat Genet 21 1999 103 107
104. S.D. Gore, S. Baylin, and E. Sugar Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms Cancer Res 66 2006 6361 6369
105. W. Blum, R.B. Klisovic, and B. Hackanson Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia J Clin Oncol 25 2007 3884 3891
106. Z.S. Thomas Prebet, Maria E. Figueroa, Rhett Ketterling on behalf of the Eastern Cooperative Oncology Group and North American Leukemia intergroup Prolonged administration of Azacitidine with or without Entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: Results of the US Leukemia Intergroup trial E1905 J Clin Oncol 32 2014 1242 1248
107. G. Garcia-Manero, F.P. Tambaro, and N.B. Bekele Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome J Clin Oncol 30 2012 2204 2210
108. T.M. Kadia, H. Yang, and A. Ferrajoli A phase I study of vorinostat in combination with idarubicin in relapsed or refractory leukaemia Br J Haematol 150 2010 72 82
109. B. Sanchez-Gonzalez, H. Yang, and C. Bueso-Ramos Antileukemia activity of the combination of an anthracycline with a histone deacetylase inhibitor Blood 108 2006 1174 1182
110. A.J. Deshpande, L. Chen, and M. Fazio Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l Blood 121 2013 2533 2541
111. S.R. Daigle, E.J. Olhava, and C.A. Therkelsen Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor Cancer Cell 20 2011 53 65
112. S.R. Daigle, E.J. Olhava, and C.A. Therkelsen Potent inhibition of DOT1L as treatment of MLL-fusion leukemia Blood 122 2013 1017 1025
113. S.N. Dinner, F.J. Giles, and J.K. Altman New strategies for relapsed acute myeloid leukemia: fertile ground for translational research Curr Opin Hematol 21 2014 79 86
114. A. Yokoyama, T.C. Somervaille, K.S. Smith, O. Rozenblatt-Rosen, M. Meyerson, and M.L. Cleary The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis Cell 123 2005 207 218
115. C. Caslini, Z. Yang, M. El-Osta, T.A. Milne, R.K. Slany, and J.L. Hess Interaction of MLL amino terminal sequences with menin is required for transformation Cancer Res 67 2007 7275 7283
116. Y.X. Chen, J. Yan, and K. Keeshan The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression Proc Natl Acad Sci U S A 103 2006 1018 1023
117. J. Grembecka, A.M. Belcher, T. Hartley, and T. Cierpicki Molecular basis of the mixed lineage leukemia-menin interaction: implications for targeting mixed lineage leukemias J Biol Chem 285 2010 40690 40698
118. S. He, T.J. Senter, and J. Pollock High-affinity small-molecule inhibitors of the menin-mixed lineage leukemia (MLL) interaction closely mimic a natural protein-protein interaction J Medicinal Chemistry 57 2014 1543 1556
119. J. Grembecka, S. He, and A. Shi Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia Nat Chem Biol 8 2012 277 284
120. F. Wang, J. Travins, and B. DeLaBarre Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation Science 340 2013 622 626
121. D. Rohle, J. Popovici-Muller, and N. Palaskas An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells Science 340 2013 626 630
122. M.I. Davis, S. Gross, and M. Shen Biochemical, cellular and biophysical characterization of a potent inhibitor of mutant isocitrate dehydrogenase IDH1 J Biol Chem 289 2014 13717 13725
123. A. Chaturvedi, M.M. Araujo Cruz, and N. Jyotsana Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML Blood 122 2013 2877 2887
124. A. Sanyal, B.R. Lajoie, G. Jain, and J. Dekker The long-range interaction landscape of gene promoters Nature 489 2012 109 113
125. J. Dekker, K. Rippe, M. Dekker, and N. Kleckner Capturing chromosome conformation Science 295 2002 1306 1311