RUNX1 meets MLL: Epigenetic regulation of hematopoiesis by two leukemia genes

Leukemia

Volumn 27, Issue 9, 2013, Pages 1793-1802

  Koh, C P ^a   Wang, C Q ^a,b   Ng, C E L ^a   Ito, Y ^a,b   Araki, M ^a   Tergaonkar, V ^b   Huang, G ^c   Osato, M ^a,b,d,e  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Singapore)

^c CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^d INSTITUTE OF BIOENGINEERING AND NANOTECHNOLOGY   (Singapore)

^e TOHOKU UNIVERSITY   (Japan)

Author keywords

AML1; epigenetic regulation; MLL; RUNX1

Indexed keywords

MIXED LINEAGE LEUKEMIA PROTEIN; TRANSCRIPTION FACTOR RUNX1;

DNA BINDING; EPIGENETIC REPRESSION; GEL MOBILITY SHIFT ASSAY; GENE MUTATION; HEMATOPOIESIS; HISTONE MODIFICATION; HUMAN; LEUKEMIA; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; REGULATOR GENE; REVIEW; TUMOR GENE;

CORE BINDING FACTOR ALPHA 2 SUBUNIT; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, LEUKEMIC; HEMATOPOIESIS; HUMANS; LEUKEMIA; MYELOID-LYMPHOID LEUKEMIA PROTEIN; POINT MUTATION; PROTEIN BINDING;

EID: 84883740586     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2013.200     Document Type: Review

References (97)

1. Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997; 278: 1059-1064. (Pubitemid 27517875)
2. Grossmann V, Schnittger S, Kohlmann A, Eder C, Roller A, Dicker F et al. A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 2012; 120: 2963-2972.
3. Steudel C, Wermke M, Schaich M, Schakel U, Illmer T, Ehninger G et al. Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes Chromosomes Cancer 2003; 37: 237-251. (Pubitemid 36667562)
4. Schnittger S, Dicker F, Kern W, Wendland N, Sundermann J, Alpermann T et al. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 2011; 117: 2348-2357.
5. Osato M. Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia. Oncogene 2004; 23: 4284-4296. (Pubitemid 38765137)
6. Harada H, Harada Y, Niimi H, Kyo T, Kimura A, Inaba T. High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia. Blood 2004; 103: 2316-2324. (Pubitemid 38326252)
7. Kuo MC, Liang DC, Huang CF, Shih YS, Wu JH, Lin TL et al. RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia 2009; 23: 1426-1431.
8. Mitani K, Ogawa S, Tanaka T, Miyoshi H, Kurokawa M, Mano H et al. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J 1994; 13: 504-510.
9. Romana SP, Mauchauffe M, Le Coniat M, Chumakov I, Le Paslier D, Berger R et al. The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood 1995; 85: 3662-3670.
10. Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J et al. New insights to the MLL recombinome of acute leukemias. Leukemia 2009; 23: 1490-1499.
11. Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood 2000; 96: 24-33. (Pubitemid 30456446)
12. Taki T, Ida K, Bessho F, Hanada R, Kikuchi A, Yamamoto K et al. Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia. Leukemia 1996; 10: 1303-1307. (Pubitemid 26261426)
13. Motoda L, Osato M, Yamashita N, Jacob B, Chen LQ, Yanagida M et al. Runx1 protects hematopoietic stem/progenitor cells from oncogenic insult. Stem Cells 2007; 25: 2976-2986. (Pubitemid 350294422)
14. Okuda T, van Deursen J, Hiebert SW, Grosveld G, Downing JR. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 1996; 84: 321-330. (Pubitemid 26042836)
15. Jacob B, Osato M. Stem cell exhaustion and leukemogenesis. J Cell Biochem 2009; 107: 393-399.
16. Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. EMBO J 2001; 20: 723-733. (Pubitemid 32167637)
17. Ito Y. Molecular basis of tissue-specific gene expression mediated by the runt domain transcription factor PEBP2/CBF. Genes Cells 1999; 4: 685-696. (Pubitemid 30053316)
18. Kanno T, Kanno Y, Chen LF, Ogawa E, Kim WY, Ito Y. Intrinsic transcriptional activation-inhibition domains of the polyomavirus enhancer binding protein 2/core binding factor alpha subunit revealed in the presence of the beta subunit. Mol Cell Biol 1998; 18: 2444-2454. (Pubitemid 28183414)
19. Ito Y. Oncogenic potential of the RUNX gene family: 'overview'. Oncogene 2004; 23: 4198-4208. (Pubitemid 38765135)
20. Yoshimi M, Goyama S, Kawazu M, Nakagawa M, Ichikawa M, Imai Y et al. Multiple phosphorylation sites are important for RUNX1 activity in early hematopoiesis and T-cell differentiation. Eur J Immunol 2012; 42: 1044-1050.
21. Michaud J, Wu F, Osato M, Cottles GM, Yanagida M, Asou N et al. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Blood 2002; 99: 1364-1372. (Pubitemid 34547093)
22. Zeng C, van Wijnen AJ, Stein JL, Meyers S, Sun W, Shopland L et al. Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proc Natl Acad Sci USA 1997; 94: 6746-6751. (Pubitemid 27281935)
23. Speck NA, Gilliland DG. Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer 2002; 2: 502-513. (Pubitemid 37328932)
24. Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA 1991; 88: 10431-10434. (Pubitemid 21915849)
25. Nucifora G, Begy CR, Erickson P, Drabkin HA, Rowley JD. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc Natl Acad Sci USA 1993; 90: 7784-7788. (Pubitemid 23250035)
26. Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P et al. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci USA 1995; 92: 4917-4921.
27. Osato M, Ito Y. Increased dosage of the RUNX1/AML1 gene: a third mode of RUNX leukemia? Crit Rev Eukar Gene Expr 2005; 15: 217-228.
28. Watson MS, Carroll AJ, Shuster JJ, Steuber CP, Borowitz MJ, Behm FG et al. Trisomy 21 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study (8602). Blood 1993; 82: 3098-3102. (Pubitemid 23334937)
29. Ferro MT, Hernaez R, Sordo MT, Garcia-Sagredo JM, Garcia-Miguel P, Fernandez Guijarro M et al. Chromosome 21 tandem repetition and AML1 (RUNX1) gene amplification. Cancer Genet Cytogenet 2004; 149: 11-16. (Pubitemid 38177552)
30. Shinawi M, Erez A, Shardy DL, Lee B, Naeem R, Weissenberger G et al. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 2008; 112: 1042-1047.
31. Lindstrand A, Malmgren H, Sahlen S, Schoumans J, Nordgren A, Ergander U et al. Detailed molecular and clinical characterization of three patients with 21q deletions. Clin Genet 2010; 77: 145-154.
32. Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T et al. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2alphaB gene associated with myeloblastic leukemias. Blood 1999; 93: 1817-1824. (Pubitemid 29128481)
33. Osato M, Yanagida M, Shigesada K, Ito Y. Point mutations of the RUNx1/AML1 gene in sporadic and familial myeloid leukemias. Int J Hematol 2001; 74: 245-251. (Pubitemid 33760078)
34. Niimi H, Harada H, Harada Y, Ding Y, Imagawa J, Inaba T et al. Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations. Leukemia 2006; 20: 635-644.
35. Taketani T, Taki T, Takita J, Ono R, Horikoshi Y, Kaneko Y et al. Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome. Leukemia 2002; 16: 1866-1867.
36. Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 1999; 23: 166-175. (Pubitemid 29455388)
37. Gelsi-Boyer V, Trouplin V, Adelaide J, Aceto N, Remy V, Pinson S et al. Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes. BMC Cancer 2008; 8: 299.
38. Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C. New mechanisms of AML1 gene alteration in hematological malignancies. Leukemia 2003; 17: 9-16. (Pubitemid 36175882)
39. Della Gatta G, Palomero T, Perez-Garcia A, Ambesi-Impiombato A, Bansal M, Carpenter ZW et al. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med 2012; 18: 436-440.
40. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012; 481: 157-163.
41. Grossmann V, Kern W, Harbich S, Alpermann T, Jeromin S, Schnittger S et al. Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia. Haematologica 2011; 96: 1874-1877.
42. Jongmans MC, Kuiper RP, Carmichael CL, Wilkins EJ, Dors N, Carmagnac A et al. Novel RUNX1 mutations in familial platelet disorder with enhanced risk for acute myeloid leukemia: clues for improved identification of the FPD/AML syndrome. Leukemia 2010; 24: 242-246.
43. Liu P, Tarle SA, Hajra A, Claxton DF, Marlton P, Freedman M et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 1993; 261: 1041-1044. (Pubitemid 23300863)
44. Castilla LH, Wijmenga C, Wang Q, Stacy T, Speck NA, Eckhaus M et al. Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell 1996; 87: 687-696. (Pubitemid 26386942)
45. Tahirov TH, Inoue-Bungo T, Morii H, Fujikawa A, Sasaki M, Kimura K et al. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Cell 2001; 104: 755-767. (Pubitemid 32241025)
46. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y et al. Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Am J Hum Genet 2002; 71: 724-738. (Pubitemid 135750507)
47. Khan M. Interplay of protein misfolding pathway and unfolded-protein response in acute promyelocytic leukemia. Expert Rev Proteomics 2010; 7: 591-600.
48. Biggs JR, Peterson LF, Zhang Y, Kraft AS, Zhang DE. AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation of AML1/RUNX1 by the anaphase-promoting complex. Mol Cell Biol 2006; 26: 7420-7429. (Pubitemid 44547694)
49. Wang S, Zhang Y, Soosairajah J, Kraft AS. Regulation of RUNX1/AML1 during the G2/M transition. Leuk Res 2007; 31: 839-851. (Pubitemid 46855893)
50. Francis NJ, Kingston RE. Mechanisms of transcriptional memory. Nat Rev Mol Cell Biol 2001; 2: 409-421. (Pubitemid 33680580)
51. Takeda S, Chen DY, Westergard TD, Fisher JK, Rubens JA, Sasagawa S et al. Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell cycle progression. Genes Dev 2006; 20: 2397-2409. (Pubitemid 44320388)
52. Yokoyama A, Cleary ML. Menin critically links MLL proteins with LEDGF on cancerassociated target genes. Cancer Cell 2008; 14: 36-46. (Pubitemid 351885493)
53. Birke M, Schreiner S, Garcia-Cuellar MP, Mahr K, Titgemeyer F, Slany RK. The MT domain of the proto-oncoprotein MLL binds to CpG-containing DNA and discriminates against methylation. Nucleic Acids Res 2002; 30: 958-965. (Pubitemid 34679664)
54. Dou Y, Milne TA, Tackett AJ, Smith ER, Fukuda A, Wysocka J et al. Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 2005; 121: 873-885. (Pubitemid 40806419)
55. Southall SM, Wong PS, Odho Z, Roe SM, Wilson JR. Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks. Mol Cell 2009; 33: 181-191.
56. Sierra J, Yoshida T, Joazeiro CA, Jones KA. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev 2006; 20: 586-600. (Pubitemid 43345324)
57. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol 2004; 24: 5639-5649. (Pubitemid 38787950)
58. Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D, Allis CD et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell 2002; 10: 1107-1117. (Pubitemid 35453828)
59. Zhang Y, Chen A, Yan XM, Huang G. Disordered epigenetic regulation in MLLrelated leukemia. Int J Hematol 2012; 96: 428-437.
60. Super HJ, McCabe NR, Thirman MJ, Larson RA, Le Beau MM, Pedersen-Bjergaard J et al. Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II. Blood 1993; 82: 3705-3711. (Pubitemid 24006054)
61. Domer PH, Head DR, Renganathan N, Raimondi SC, Yang E, Atlas M. Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11). Leukemia 1995; 9: 1305-1312.
62. Meyer C, Schneider B, Jakob S, Strehl S, Attarbaschi A, Schnittger S et al. The MLL recombinome of acute leukemias. Leukemia 2006; 20: 777-784.
63. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S et al. Hematologic malignancies with t(4;11)(q21;q23)-a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia 1998; 12: 779-787. (Pubitemid 28220836)
64. Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N et al. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci USA 1993; 90: 4631-4635. (Pubitemid 23148959)
65. Kroon E, Krosl J, Thorsteinsdottir U, Baban S, Buchberg AM, Sauvageau G. Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b. EMBO J 1998; 17: 3714-3725. (Pubitemid 28327389)
66. Magli MC, Largman C, Lawrence HJ. Effects of HOX homeobox genes in blood cell differentiation. J Cell Physiol 1997; 173: 168-177. (Pubitemid 27481125)
67. Drabkin HA, Parsy C, Ferguson K, Guilhot F, Lacotte L, Roy L et al. Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia. Leukemia 2002; 16: 186-195. (Pubitemid 34145135)
68. Schraets D, Lehmann T, Dingermann T, Marschalek R. MLL-mediated transcriptional gene regulation investigated by gene expression profiling. Oncogene 2003; 22: 3655-3668. (Pubitemid 36765325)
69. Ross ME, Mahfouz R, Onciu M, Liu HC, Zhou X, Song G et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood 2004; 104: 3679-3687. (Pubitemid 39564445)
70. Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002; 30: 41-47.
71. Rozovskaia T, Feinstein E, Mor O, Foa R, Blechman J, Nakamura T et al. Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4: 11) abnormality. Oncogene 2001; 20: 874-878. (Pubitemid 32198181)
72. Caligiuri MA, Strout MP, Schichman SA, Mrozek K, Arthur DC, Herzig GP et al. Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11. Cancer Res 1996; 56: 1418-1425. (Pubitemid 26080988)
73. Schichman SA, Caligiuri MA, Gu Y, Strout MP, Canaani E, Bloomfield CD et al. ALL-1 partial duplication in acute leukemia. Proc Natl Acad Sci USA 1994; 91: 6236-6239. (Pubitemid 24188318)
74. Schnittger S, Kinkelin U, Schoch C, Heinecke A, Haase D, Haferlach T et al. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML. Leukemia 2000; 14: 796-804. (Pubitemid 30235055)
75. Bacher U, Haferlach T, Kern W, Haferlach C, Schnittger S. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007; 92: 744-752. (Pubitemid 350155299)
76. Shih LY, Liang DC, Fu JF, Wu JH, Wang PN, Lin TL et al. Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement. Leukemia 2006; 20: 218-223.
77. Basecke J, Whelan JT, Griesinger F, Bertrand FE. The MLL partial tandem duplication in acute myeloid leukaemia. Brit J Haematol 2006; 135: 438-449. (Pubitemid 44583410)
78. Tang JL, Hou HA, Chen CY, Liu CY, Chou WC, Tseng MH et al. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 2009; 114: 5352-5361.
79. Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S et al. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood 2012; 120: 1118-1129.
80. Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M. Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. EMBO J 2001; 20: 7184-7196. (Pubitemid 34062310)
81. Kitabayashi I, Yokoyama A, Shimizu K, Ohki M. Interaction and functional cooperation of the leukemia-associated factors AML1 and p300 in myeloid cell differentiation. EMBO J 1998; 17: 2994-3004. (Pubitemid 28254372)
82. Taniuchi I, Littman DR. Epigenetic gene silencing by Runx proteins. Oncogene 2004; 23: 4341-4345. (Pubitemid 38758600)
83. Herglotz J, Kuvardina ON, Kolodziej S, Kumar A, Hussong H, Grez M et al. Histone arginine methylation keeps RUNX1 target genes in an intermediate state. Oncogene 2012; 32: 1-11.
84. Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S et al. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Proc Natl Acad Sci USA 1998; 95: 11590-11595. (Pubitemid 28460459)
85. Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW. A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. J Biol Chem 2000; 275: 651-656. (Pubitemid 30039030)
86. Chakraborty S, Sinha KK, Senyuk V, Nucifora G. SUV39H1 interacts with AML1 and abrogates AML1 transactivity. AML1 is methylated in vivo. Oncogene 2003; 22: 5229-5237. (Pubitemid 37056085)
87. Gutierrez MI, Siraj AK, Bhargava M, Ozbek U, Banavali S, Chaudhary MA et al. Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup. Leukemia 2003; 17: 1845-1850. (Pubitemid 37185261)
88. Maiques-Diaz A, Chou FS, Wunderlich M, Gomez-Lopez G, Jacinto FV, Rodriguez-Perales S et al. Chromatin modifications induced by the AML1-ETO fusion protein reversibly silence its genomic targets through AML1 and Sp1 binding motifs. Leukemia 2012; 26: 1329-1337.
89. Stumpel DJ, Schneider P, Seslija L, Osaki H, Williams O, Pieters R et al. Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia. Leukemia 2012; 26: 682-692.
90. Lasa A, Carnicer MJ, Aventin A, Estivill C, Brunet S, Sierra J et al. MEIS 1 expression is downregulated through promoter hypermethylation in AML1-ETO acute myeloid leukemias. Leukemia 2004; 18: 1231-1237. (Pubitemid 39023133)
91. Huang G, Zhao X, Wang L, Elf S, Xu H, Sashida G et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood 2011; 118: 6544-6552.
92. Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z et al. PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 2008; 40: 51-60.
93. Ng CE, Yokomizo T, Yamashita N, Cirovic B, Jin H, Wen Z et al. A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells. Stem Cells 2010; 28: 1869-1881.
94. Shih AH, Abdel-Wahab O, Patel JP, Levine RL. The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer 2012; 12: 599-612.
95. Taniuchi I, Osato M, Ito Y. Runx1: no longer just for leukemia. EMBO J 2012; 31: 4098-4099.
96. Asou N, Yanagida M, Huang L, Yamamoto M, Shigesada K, Mitsuya H et al. Concurrent transcriptional deregulation of AML1/RUNX1 and GATA factors by the AML1-TRPS1 chimeric gene in t(8;21)(q24;q22) acute myeloid leukemia. Blood 2007; 109: 4023-4027. (Pubitemid 46641757)
97. Huang L, Osato M, Yanagida M, Yamashita N, Ito Y. The myeloid features of BXH2 leukemias may result from the lack of one copy of the repetitive sequence in the long terminal repeat viral enhancer. Int J Hematol 2007; 85: 170-172. (Pubitemid 46365556)