Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/ progenitor cells: Therapeutic potential of cell reprogramming

Leukemia

Volumn 22, Issue 8, 2008, Pages 1503-1518

  Zardo, G ^a,b   Cimino, G ^a   Nervi, C ^a,b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b San Raffaele Biomedical Park Foundation   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; APICIDIN; AZACITIDINE; BENZAMIDE; BONE MORPHOGENETIC PROTEIN; BUTAMIRATE; DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE INHIBITOR; HISTONE DEACETYLASE; HISTONE DEACETYLASE INHIBITOR; HISTONE METHYLTRANSFERASE; HOX PROTEIN; METHYL CPG BINDING PROTEIN; MIXED LINEAGE LEUKEMIA PROTEIN; MYC PROTEIN; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; OCTAMER TRANSCRIPTION FACTOR 4; PHENYLBUTAZONE; POLYCOMB GROUP PROTEIN; RETINOIC ACID; ROMIDEPSIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR RUNX1; TRANSCRIPTION FACTOR SOX2; TRICHOSTATIN A; UNINDEXED DRUG; VALPROIC ACID; VORINOSTAT; WNT PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CHROMATIN STRUCTURE; COMBINATION CHEMOTHERAPY; DNA BINDING; DNA METHYLATION; DNA SYNTHESIS; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG MECHANISM; EMBRYONIC STEM CELL; EPIGENETICS; GENE EXPRESSION REGULATION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HUMAN; LEUKEMIA CELL; LEUKEMOGENESIS; LOW DRUG DOSE; MONOTHERAPY; MUTATION; MYELODYSPLASTIC SYNDROME; NONHODGKIN LYMPHOMA; NONHUMAN; PLASTICITY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN MODIFICATION; REVIEW; TRANSCRIPTION REGULATION; UNSPECIFIED SIDE EFFECT;

EID: 49449100095     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2008.141     Document Type: Review

References (206)

1. Holliday R. The inheritance of epigenetic defects. Science 1987, 238: 163-170.
2. Grewal SI, Moazed D. Heterochromatin and epigenetic control of gene expression. Science 2003; 301: 798-802.
3. Lanzuolo C, Orlando V. The function of the epigenome in cell reprogramming. Cell Mol Life Sci 2007; 64: 1043-1062.
4. Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and gene silencing. Cell 2007; 128: 763-776.
5. Turner BM. Defining an epigenetic code. Nat Cell Biol 2007; 9 2-6.
6. Downs JA, Nussenzweig. MC, Nussenzweig A. Chromatin dynamics and the preservation of genetic information. Nature 2007; 447: 951-958.
7. Fischle W, Wang Y, Allis CD. Histone and chromatin cross-talk. Curr Opin Cell Biol 2003; 15: 172-183.
8. Goll MG, Bestor TH. Eukaryotic cytosine methyltransferases. Annu Rev Biochem 2005; 74: 481-514.
9. Clark SJ. Action at a distance: Epigenetic silencing of large chromosomal regions in carcinogenesis. Hum Mol Genet 2007; 16 (Spec No 1): R88-R95.
10. Miranda TB, Jones PA. DNA methylation: The nuts and bolts of repression. J Cell Physiol 2007; 213: 384-390.
11. Okano M, Xie S, Li E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat Genet 1998; 19: 219-220
12. Aapola U, Lyle R, Krohn K, Antonarakis SE, Peterson P. Isolation and initial characterization of the mouse Dnmt3 I gene. Cvtogenet Cell. Genet 2001; 92: 122-126.
13. Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science 2001; 294 2536-2539.
14. Chedin F, Lieber MR, Hsieh CL. The DNA methyltransferase like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci USA 2002; 99: 16916-16921.
15. Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 2007; 448: 714-717.
16. Yoo CB, Jones PA. Epigenetic therapy of cancer: Past, present and future. Nat Rev Drug Discov 2006; 5: 37-50.
17. Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 2002; 99: 3740-3745.
18. Smit AF, Riggs AD. Tiggers and DNA transposon fossils in the human genome. Proc Natl Acad Sci USA 1996; 93: 1443-1448.
19. Kass SU, Landsberger N, Wolffe AP. DNA methylation directs a time-dependent repression of transcription initiation. Curr Biol 1997; 7: 157-165.
20. Song F, Smith JF, Kimura MT, Morrow AD, Matsuyama T, Nagase H et al Association of tissue-specific differentially methylated regions (TDMs) with differential gene expression. Proc Natl Acad Sci USA 2005; 102: 3336-3341.
21. Klose RJ, Bird AP. Genomic DNA methylation: The mark and its mediators. Trends Biochem Sci 2006; 31: 89-97.
22. Yang XJ. Lysine acetylation and the bromodomain: A new partnership for signaling. Bioessays 2004; 26: 1076-1087.
23. Roth SY, Denu JM, Allis CD. Historic acetyltransferases. Annu Rev Biochem 2001; 70: 81-120.
24. Gregorotti IV, Lee YM, Goodson HV, Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J Mol Biol 2004; 338: 17-31.
25. Berger SL. Histone modifications in transcriptional regulation. Curr Opin Genet Dev 2002; 12: 142-148.
26. Kouzarides T. Histone methylation in transcriptional control. Curr Opin Genet Dev 2002; 12: 198-209.
27. Bannister AJ, Kouzarides T. Histone methylation: Recognizing the methyl mark. Methods Enzymol 2004; 376: 269-288.
28. Kubicek S, O'Sullivan RJ, August EM, Hickey ER, Zhang Q, Teodoro ML et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25: 473-481.
29. Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 2007; 25: 1-14.
30. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM et al Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 2006; 125: 301-313.
31. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP et al Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005; 122: 947-956.
32. Schwartz YB, Pirrotta V. Polycomb silencing mechanisms and the management of genomic programmes. Nat Rev Genet 2007; 8: 9-22.
33. Otte AP, Kwaks TH. Gene repression by Polycomb group protein complexes: a distinct complex for every occasion? Curr Opin Genet Dev 2003; 13: 448-454.
34. Czermin B, Melfi R, McCabe D, Seitz V, Imhof A, Pirrotta V. Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell 2002; 111 185-196.
35. Fischle W, Wang Y, Jacobs SA, Kim Y, Allis CD, Khorasanizadeh S. Molecular basis for the discrimination of repressive methyllysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev 2003; 17: 1870-1881.
36. Wang H, Wang L, Erdjument-Bromage H, Vidar M, Tempst P, Jones RS et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature 2004; 431: 873-878.
37. Dellino GI, Schwartz YB, Farkas G, McCabe D, Elgin SC, Pirrotta V. Polycomb silencing blocks transcription initiation. Mol Cell 2004; 13: 887-893.
38. Francis NJ, Kingston RE. Mechanisms of transcriptional memory. Nat Rev Mol Cell Biol 2001; 2: 409-421.
39. Daujat S, Zeissler U, Waldmann T, Happel N, Schneider R. HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem 2005; 280 38090-38095.
40. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006; 439: 871-874.
41. Mohd-Sarip A, van der Knaap JA, Wyman C, Kanaar R, Schedl P, Verrijzer CP. Architecture of a polycomb nucleoprotein complex. Mol Cell 2006; 24: 91-100.
42. Beisel C, Imhof A, Greene J, Kremmer E, Sauer F. Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1. Nature 2002; 419: 857-862.
43. Xia ZB, Anderson M, Diaz MO, Zeleznik L. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci USA 2003; 100: 8342-8347.
44. Ernst P, Mahon M, Davidson AJ, Zon LI, Korsmeyer SJ. An Mll-dependent Hox program drives hematopoietic progenitor expansion. Curr Biol 2004; 14: 2063-2069.
45. 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.
46. 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.
47. Milne TA, Martin ME, Brock HW, Slany RK, Hess JL. Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9 locus, promoting transcription and multiple histone modifications. Cancer Res 2005; 65: 11367-11374.
48. Guenther MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani F et al. Global' and Hox-specific roles for the MLL1 methyltransferase. Proc Natl Acad Sci USA 2005; 102: 8603-8608.
49. Niwa H. How is pluripotency, determined and maintained? Development 2007; 134: 635-646.
50. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
51. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2007; 2: 3081-3089.
52. Jaenisch R, Young R. Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell 2008; 132: 567-582.
53. Meshorer E, Misteli T. Chromatin in pluripotent embryonic stem cells and differentiation. Nat Rev Mol Cell Biol 2006; 7: 540-546.
54. Brown DT. Histone H1 and the dynamic regulation of chromatin function. Biochem Cell Biol 2003; 81: 221-227.
55. Phair RD, Scaffidi, P, Elbi C, Vecerova J, Dey A, Ozato K et al. Global nature of dynamic protein-chromatin interactions in vivo: three-dimensional genome scanning and dynamic interaction networks of chromatin proteins. Mol Cell Biol 2004; 24: 6393-6402.
56. Wiblin AE, Cui W, Clark AJ, Bickmore WA. Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells. J Cell Sci 2005; 118: 3861-3868.
57. Lee JH, Hart SR, Skalnik DG. Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis 2004; 38; 32-38.
58. Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM et al Chromatin signatures of pluripotent cell lines. Nat Cell Biol 2006; 8: 532-538.
59. Bernstein BE, Mikkelsen TS, Xie X, Kamall M, Huebert DJ, Cuff J et al A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 2006; 125: 315-326.
60. Guccione E, Martinato F, Finocchiaro G, Luzi L, Tizzoni L, Dall O et al. Myc-binding-site recognition in the human genome is determined by chromatin context. Nat Cell Biol 2006; 8: 764-770.
61. Jackson-Grusby L, Beard C, Possemato Tudor M, Fambrough D, Csankovszki G et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet 2001; 27: 31-39.
62. Jackson M, Krassowska A, Gilbert N, Chevassut T, Forrester L, Ansell J et al. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol Cell Biol 2004; 24: 8862-8871.
63. Blelloch R, Wang Z, Meissner A, Pollard S, Smith A, Jaenisch R. Reprogramming efficiency following somatic cell nuclear transfer is influenced by the differentiation and methylation state of the donor nucleus. Stem Cells 2006; 24: 2007-2013.
64. Goren A, Cedar H. Replicating by the clock. Nat Rev Mol Cell Biol 2003; 4: 25-32.
65. Perry P, Sauer S, Billon N, Richardson WD, Spivakov M, Warnes G et al A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction. Cell Cycle 2004; 3 1645-1650.
66. Williams RR, Azuara V, Perry P, Sauer S, Dvorkina M, Jorgensen H et al. Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 2006; 119: 132-140.
67. Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L et al. A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 2007; 39: 237-242.
68. Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H et al. Role of histone H3 lysine 27 methylation in X inactivation. Science 2003; 300: 131-135.
69. Koyanagi M, Baguet A, Martens J, Margueron R, Jenuwein T, Bix M. EZH2 and histone 3 trimethyl lysine 27 aasociated with Il4 and Il13 gene silencing in Th1 cells. J Biol Chem 2005; 280: 31470-31477.
70. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 2001; 292: 110-113.
71. Jiang G, Yang F, Sanchez C, Ehrlich M. Histone modification in constitutive heterochromatin versus unexpressed euchromatin in human cells. J Cell Biochem 2004; 93: 286-300.
72. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006; 441: 349-353.
73. Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K. Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 2006; 20: 1123-1136.
74. Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 2006; 6: 846-856.
75. Akashi K. Lineage promiscuity and plasticity in hematopoietic development. Ann N Y Acad Sci 2005; 1044: 125-131.
76. Zhu J, Emerson SP. Hematopoietic cytokines, transcription factors and lineage commitment. Oncogene 2002; 21: 3295-3313.
77. Mikkola HK, Orkin SH. The journey of developing hematopoietic stem cells. Development 2006; 133: 3733-3744.
78. Tenen DG. Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer 2003; 3: 89-101.
79. Bonifer C. Epigenetic plasticity of hematopoietic cells. Cell Cycle 2005; 4: 211-214.
80. Escamilla-Del-Arenal M, Recillas-Targa F. GATA-1 modulates the chromatin structure and activity of the chicken alpha-globin 3′ enhancer. Mol Cell Biol 2008; 28: 575-586.
81. Layon ME, Ackley CJ, West RJ, Lowrey CH. Expression of GATA-1 in a non-hematopoietic cell line induces beta-globin locus control region chromatin structure remodeling and an erythroid pattern of gene expression. J Mol Biol 2007; 366: 737-744.
82. Levings PP, Zhou Z, Vieira KF, Crusselle-Davis VJ, Bungert J. Recruitment of transcription complexes to the beta-globin locus control region and transcription of hypersensitive site 3 prior to erythroid differentiation of murine embryonic stern cells. FEBS J 2006; 273: 746-755.
83. Attema JL, Papathanasiou P, Forsberg EC, Xu J, Smale ST, Weissman IL. Epigenetic characterization of hematopoietic stem cell differentiation using miniChlP and bisulfite sequencing analysis. Proc Natl Acad Sci USA 2007; 104: 12371-12376.
84. Stopka T, Amanatullah DF, Papetti M, Skoultchi AI. PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure. EM80 J 2005; 24: 3712-3723.
85. Huang S, Brandt SJ, mSin3A regulates murine erythroleukemia cell differentiation through association with the TAL1 (or SCL) transcription factor. Mol Cell Biol 2000; 20: 2248-2259.
86. Friedman AD. Transcriptional control oi granulocyte and monocyte development. Oncogene 2007; 26: 6816-6828.
87. Ivascu C, Wasserkort R, Lesche R, Dong J, Stein H, Thiel A et al. DNA methylation profiling of transcriptidn factor genes in normal lymphocyte development and lymphomas. Int J Biochem Cell Biol 2007; 39: 1523-1538.
88. Tatetsu H, Ueno S, Hata H, Yamada Y, Takeya M, Mitsuya H et al. Down-regulation of PU.1 by methylation of distal regulatory elements and the promoter is required for myeloma cell growth. Cancer Res 2007; 67: 5328-5336.
89. Sherr CJ. Colony-stimulating factor-1 receptor. Blood 1990; 75 1-12.
90. Bonifer C, Hume DA. The transcriptional regulation of the colony-stimulating factor 1 receptor (csf1r) gene during hematopoiesis. Front Biosci 2008; 13: 549-560.
91. Krysinska H, Hoogenkamp M, Ingram R, Wilson N, Tagoh H, Laslo P et al A two-step, PU.1-dependent mechanism for developmentally regulated chromatin remodeling and transcription of the c-fms gene. Mol Cell Biol 2007; 27: 878-887.
92. Plachetka A, Chayka O, Wilczek C, Melnik S, Bonifer C, Klempnauer KH. C/ EBPbeta induces chromatin opening at a cell-type-specific enhancer. Mol Cell Biol 2008; 28: 2102-2112.
93. Rosenbauer F, Tenen DG. Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol 2007; 7: 105-117.
94. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128 683-692.
95. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 2007; 8: 286-298.
96. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Calton DA, Gralnick HR et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 1985; 103: 620-625.
97. Moe-Behrens GH, Pandolfi PP. Targeting aberrant transcriptional repression in acute myeloid leukemia. Rev Clin Exp Hematol 2003; 7: 139-159.
98. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006; 6: 38-51.
99. Di Croce L. Chromatin modifying activity of leukaemia associated fusion proteins. Hum Mol Genet 2005; 14 (Spec No 1): R77-R84.
100. Melnick A. Predicting the effect of transcription therapy in hematologic malignancies. Leukemia 2005; 19: 1109-1117.
101. Glass CK, Rosenfeld MG. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000; 14: 121-141.
102. Chambon P. A decade of molecular biology of retinoic acid receptors. FASEB J 1996; 10: 940-954.
103. Villa R, Morey L, Raker VA, Buschbeck M, Gutierrez A, De Santis F et al. The methyl-CpG binding protein MBD1 is required for PML-RARalpha function. Proc Natl Acad Sci USA 2006; 103: 1400-1405.
104. Carbone R, Botrugno OA, Ronzoni S, Insinga A, Di Croce L, Pelicci PG et al. Recruitment of the histone methyltransferase SUV39H1 and its role in the oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion protein. Mol Cell Biol 2006; 26: 1288-1296.
105. Fazi F, Zardo G, Gelmetti V, Travaglini L, Ciolfi A, Di Croce L et al Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia. Blood 2007; 109: 4432-4440.
106. Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M et al Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 2002; 295: 1079-1082.
107. Villa R, Pasini D, Gutierrez A, Morey L, Occhionorelli M, Vire E et al. Role of the polycomb repressive complex 2 in acute promyelocytic leukemia. Cancer Cell 2007; 11: 513-525.
108. Zeisig BB, Kwok C, Zelent A, Shankaranarayanan P, Gronemeyer H, Dong S et al. Recruitment of RXR by homotetrameric RARalpha fusion proteins is essential for transformation. Cancer Cell 2007; 12 36-51.
109. Zhu J, Nasr R, Peres L, Riaucoux-Lormiere F, Honore N, Berthier C et al. RXR is an essential component of the oncogenic PML/RARA complex in vivo. Cancer Cell 2007; 12: 23-35.
110. Hiebert SW, Downing JR, Lenny N, Meyers S. Transcriptional regulation by the t(8;21) fusion protein, AML-1/ETO. Curr Top Microbiol Immunol 1996; 211: 253-258.
111. Look AT. Oncogenic transcription factors in the human acute leukemias. Science 1997; 278: 1059-1064.
112. Nucifora G, Birn DJ, Erickson P, Gao J, LeBeau MM, Drabkin HA et al Detection of DNA rearrangements in the AML1 and ETO loci and of an AML1/ETO fusion mRNA in patients with t(8;21) acute myeloid leukemia. Blood 1993; 81: 883-888.
113. Peterson LF, Zhang DE. The 8;21 translocation in leukemogenesis. Oncogene 2004; 23: 4255-4262.
114. Pabst T, Mueller BU, Harakawa N, Schoch C, Haferlach T, Behre G et al AML1-ETO downregulates the granulocytic differentiation factor C/ EBPalpha in t(8;21) myeloid leukemia. Nat Med 2001; 7: 444-451.
115. Fazi F, Zardo G, Gelmetti V, Travaglini L, Ciolfi A, Di Croce L et al Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia. Blood 2007; 109: 4432-4440.
116. Choi Y, Elagib KE, Delehanty LL, Goldfarb AN. Erythroid inhibition by the leukemic fusion AML1-ETO is associated with impaired acetylation of the major erythroid transcription factor GATA-1. Cancer Res 2006; 66: 2990-2996.
117. Zhang J, Kalkum M, Yamamura S, Chait BT, Roeder RG. E protein silencing by the leukemogenic AML1-ETO fusion protein. Science 2004; 305 1286-1289.
118. Fazi F, Racanicchi S, Zardo G, Starnes LM, Mancini M, Travaglini L et al. Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell 2007; 12: 457-466.
119. Nervi C, Fazi F, Grignani F. Oncoproteins, heterochromatin silencing and microRNAs: A new link for leukemogenesis. Epigenetics 2008; 3 1-4.
120. Alcalay M, Meani N, Gelmetti V, Fantozzi A, Fagioli M, Orleth A et al Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair. J Clin Invest 2003; 112 1751-1761.
121. Hess JL, Hug BA. Fusion-protein truncation provides new insights into leukemogenesis. Proc Natl Acad Sci USA 2004; 101: 16985-16986.
122. Rozman M, Camos M, Colomer D, Villamor N, Esteve J, Costa D et al. Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation. Genes Chromosomes Cancer 2004; 40: 140-145.
123. Panagopoulos I, Fioretos T, Isaksson M, Samuelsson U, Billstrom R, Strombeck B et al. Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13). Hum Mol Genet 2001; 10: 395-404.
124. Deguchi K, Ayton PM, Carapeti M, Kutok JL, Snyder CS, Williams IR et al. MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. Cancer Cell 2003; 3: 259-271.
125. Troke PJ, Kindle KB, Collins HM, Heery DM. MOZ fusion proteins in acute myeloid leukaemia. Biochem Soc Symp 2006; 73: 23-39.
126. Peters AH, O'Carroll D, Scherthan H, Mechtler K, Sauer S, Schofer C et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 2001; 107 323-337.
127. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436: 660-665.
128. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM et al. hDOT1L links histone methylation to leukemogenesis. Cell 2005; 121: 167-178.
129. Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C et al. Epigenetic stem cell signature in cancer. Nat Genet 2007; 39: 157-158.
130. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J et al. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet 2007; 39: 232-236.
131. Kirmizis A, Bartley SM, Farnham PJ. Identification of the polycomb group protein SU(Z)12 as a potential molecular target for human cancer therapy. Mol Cancer Ther 2003; 2: 113-121.
132. Van Kemenade FJ, Raaphorst FM, Blokzijl T, Fieret E, Hamer KM, Satijn DP et al. Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 2001; 97: 3896-3901.
133. Richie ER, Schumacher A, Angel JM, Holloway M, Rinchik EM, Magnuson T. The Polycomb-group gene eed regulates thymocyte differentiation and suppresses the development of carcinogen-induced T-cell lymphomas. Oncogene 2002; 21: 299-306.
134. Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A. Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia 2007; 21: 1116-1122.
135. Mohty M, Yong AS, Szydlo RM, Apperley JF, Melo JV. The polycomb group BMI1 gene is a molecular marker for predicting prognosis of chronic myeloid leukemia. Blood 2007; 110: 380-383.
136. Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003; 423: 255-260.
137. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003; 423: 302-305.
138. Jacobs JJ, Kieboom K, Marino S, dePinho RA, van Lohuizen M. The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 1999; 397: 164-168.
139. Jacobs JJ, Scheijen B, Voncken JW, Kieboom K, Berns A, van Lohuizen M. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev 1999; 13: 2678-2690.
140. Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood 2000; 96: 24-33.
141. Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S et al Cloning of ALL-1, the locus involved in leukemias with the t 4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res 1991; 51: 6712-6714.
142. Hess JL. MLL: A histone methyltransferase disrupted in leukemia. Trends Mol Med 2004; 10: 500-507.
143. Ida K, Kitabayashi I, Taky T, Taniwaki M, Novo K, Yamamoto M et al Adenovirus E1A-associated protein p300 is involved in acute myeloid leukaemia with t(11;22). Blood 1997; 90: 4699-4704.
144. Linggi B, Muller-Tidow C, van de Locht L, Hu M, Nip J, Serve H et al The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat Med 2002; 8: 743-750.
145. Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S et al All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997; 90 535-541.
146. Dorrance AM, Liu S, Yuan W, Becknell B, Arnoczky KJ, Guimond M et al Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations. J Clin Invest 2006; 116: 2707-2716.
147. Megonigal MD, Cheung NK, Rappaport EF, Nowell PC, Wilson RB, Jones DH et al. Detection of leukemia-associated MLL-GAS7 translocation early during chemotherapy with DNA topoisomerase II inhibitors. Proc Natl Acad Sci USA 2000; 97: 2814-2819.
148. Bernard OA, Mauchauffe M, Mecucci C, Van den BH, Berger R. A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene 1994; 9: 1039-1045.
149. So CW, Lin M, Ayton PM, Chen EH, Cleary ML. Dimerization contributes to oncogenic activation of MLL chimeras in acute leukemias. Cancer Cell 2003; 4: 99-110.
150. So CW, Karsunky H, Passegue E, Cozzio A, Weissman IL, Cleary ML. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell 2003; 3: 161-171.
151. So CW, Cleary ML. Common mechanism for oncogenic activation of MLL by forkhead family proteins. Blood 2003; 101: 633-639.
152. Erfurth F, Hemenway CS, de Erkenez AC, Domer PH. MLL fusion partners AF4 and AF9 interact at subnuclear foci. Leukemia 2004; 18: 92-102.
153. Zeisig DT, Bittner CB, Zeisig BB, Garcia-Cuellar MP, Hess JL, Slany RK. The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners with chromatin. Oncogene 2005; 24: 5525-5532.
154. Bitoun E, Oliver PL, Davies KE. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodelling. Hum Mol Genet 2007; 16: 92-106.
155. Zeisig BB, Milne T, Garcia-Cuellar MP, Schreiner S, Martin ME, Fuchs U et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 2004; 24: 617-628.
156. 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.
157. Moskow JJ, Bullrich F, Huebner K, Daar IO, Buchberg AM. Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice, Mol Cell Biol 1995; 15: 5434-5443.
158. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP et al Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007; 318: 1920-1923.
159. Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 2002; 109: 29-37.
160. Purton LE, Bernstein ID, Collins SJ. All-trans retinoic acid delays the differentiation of primitive hematopoietic precursors (lin-c- kit+Sca-1(+)) while enhancing the terminal maturation of committed granulocyte/monocyte progenitors. Blood 1999; 94: 483-495.
161. De Felice L, Tatarelli C, Mascolo MG, Gregorj C, Agostini F, Fiorini R et al. Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res 2005; 65: 1505-1513.
162. Milhem M, Mahmud N, Lavelle D, Araki H, DeSimone J, Saunthararajah Y et al. Modification of hematopoietic stem cell fate by 5aza 2'deoxycytidine and trichostatin A. Blood 2004; 103: 4102-4110.
163. Bug G, Gul H, Schwarz K, Pfeifer H, Kampfmann M, Zheng X et al. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res 2005; 65: 2537-2541.
164. Purton LE, Bernstein ID, Collins SJ. All-trans retinoic acid enhances the long-term repopulating activity of cultured hematopoietic stem cells. Blood 2000; 95: 470-477.
165. Melnick A, Licht JD. Deconstructing a disease: RARα, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999; 93: 3167-3215.
166. Warrell Jr RP, Frankel SR, Miller WHJ, Scheinberg DA, Itri LM, Hittelman WN et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1991; 324: 1385-1393.
167. Grignani F, De Matteis S, Nervi C, Tomassoni L, Geknetti V, Cioce M et al. Fusion proteins of the retinoic acid receptor-α recruit histone deacetylase in promyelocytic leukaemia. Nature 1998; 391: 815-818.
168. Lin RJ, Nagy L, Inoue S, Shao W, Miller WHJ, Evans RM. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 1998; 391: 811-814.
169. He LZ, Guidez F, Tribioli C, Peruzzi D, Ruthardt M, Zelent A et al Distinct interactions of PML-RARalpha and PLZF-RARalpha with co-repressors determine differential responses to RA in APL. Nat Genet 1998; 18: 126-135.
170. He LI, Tribioli C, Rivi R, Peruzzi D, Pelicci PG, Soares V et al. Acute leukemia with promyelocytic features in PML/RARα transgenic mice. Proc Natl Acad Sci USA 1997; 94: 5302-5307.
171. Sanz MA, Tallman MS, Lo-Coco F. Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia. Blood 2005; 105: 3019-3025.
172. Leone G, D'alò F, Zardo G, Voso MT, Nervi C. Epigenetic treatment of myelodysplastic syndromes and acute myeloid leukemias. Curr Med Chem 2006; 15: 1274-1287.
173. Saiki JH, Bodey GP, Hewlett JS, Amare M, Morrison FS, Wilson HE et al Effect of schedule on activity and toxicity of 5- azacytidine in acute leukemia: A Southwest Oncology Group Study. Cancer 1981; 47: 1739-1742.
174. Muller Cl, Ruter B, Koeffler HP, Lubbert M. DNA hypermethylation of myeloid cells, a novel therapeutic target in MDS and AML. Curr Pharm Biotechnol 2006; 7: 315-321.
175. Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: Studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006; 24: 3895-3903.
176. Sudan N, Rossetti JM, Shadduck RK, Latsko J, Lech JA, Kaplan RB et al Treatment of acute myelogenous leukemia with outpatient azacitidine. Cancer 2006; 107: 1839-1843.
177. Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103: 1635-1640.
178. Wijermans PW, Lubbert M, Verhoef G, Klimek V, Bosly A. An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol 2005; 84 (Suppl 1): 9-17.
179. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: A study of the cancer and leukemia group B. J Clin Oncol 2002; 20: 2429-2440.
180. Wijermans P, Lubbert M, Verhoef G, Bosly A, Ravoet C, Andre M et al Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: A multicenter phase II study in eldetly patients. J Clin Oncol 2000; 18: 956-962.
181. Lubbert M, Wijermans P, Kunzmann R, Verhoef G, Bosly A, Ravoet C et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-do5e treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 2001; 114: 349-357.
182. Esteller M. DNA methylation and cancer therapy: New developments and expectations. Curr Opin Oncol 2005; 17: 55-60.
183. Lubbert M. DNA methylation inhibitors in the treatment of leukemias, myelodysplastic syndromes and hemoglobinopathies: Clinical results and possible mechanisms of action. Curr Top Microbiol Immunol 2000; 249: 135-164.
184. Johnstone RW. Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer. Nat Rev Drug Discov 2002; 1: 287-299.
185. Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S et al Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 2001; 20: 6969-6978.
186. Nebbioso A, Clarke N, Voltz E, Germain E, Ambrosino C, Bontempo, P et al. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med 2005; 11: 77-84.
187. Insinga A, Monestiroli S, Ronzooi S, Gelmetti V, Marchesi F, Viale A et al. Inhibitors of histope deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 2005; 11: 71-76.
188. Lu Q, Yang YT,. Chen CS, Davis M, Byrd JC, Etherton MR et al. Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors. J Med Chem 2004; 4: 467-474.
189. Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays 1995; 17: 423-430.
190. Richon VM, Emiliani S, Verdin E, Webb Y, Breslow R, Rifkind RA et al A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci USA 1998; 95 3003-3007.
191. Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 1990; 265: 17174-17179.
192. O'Connor OA, Heaney ML, Schwartz L, Richardson S, Willim R, MacGregor-Cortelli B et al. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J Clin Oncol 2006; 24: 166-173.
193. Garcia-Manero G, Yang H, Bueso-Ramos C, Ferrajoli A, Cortes J, Wierda WG et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood 2008; 111: 1060-1066.
194. Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, Kelly C et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood 2007; 109 31-39.
195. Suzuki T, Ando T, Tsuchiya K, Fukazawa N, Saito A, Mariko Y et al. Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. J Med Chem 1999; 42: 3001-3003.
196. Gojo I, Jiemjit A, Trepel JB, Sparreboorn A, Figg WD, Rollins S et al Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood 2007; 109: 2781-2790.
197. Ryan QC, Headlee D, Acharya M, Sparreboorn A, Trepel JB, Ye J et al Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 2005; 23: 3912-3922.
198. Singh SB, Zink DL, Liesch JM, Mosley RT, Dombrowski AW, Bills GF et al. Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal alpha-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities. J Org Chem 2002; 67: 815-825.
199. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007; 26: 5541-5552.
200. Kuendgen A, Strupp C, Aivado M, Bernhardt A, Hildebrandt B, Haas R et al. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 2004; 104 1266-1269.
201. Kuendgen A, Knipp S, Fox F, Strupp C, Hildebrandt B, Steidl C et al Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol 2005; 84 (Suppl 13): 61-66.
202. Cimino G, Lo-Coco F, Fenu S, Travaglini L, Finolezzi E, Mancini M et al. Sequential Valproic acid/all-trans retinoic acid treatment reprograms differentiation in refractory and high-risk acute myeloid leukemia. Cancer Res 2006; 66: 8903-8911.
203. Bug G, Schwarz K; Schoch C, Kampfmann M, Henschler R, Hoelzer D et al Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia. Haematologica 2007; 92: 542-545.
204. Gore SD, Baylin S, Sugar E, Carraway H, Miller CB, Carducci M et al Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66: 6361-6369.
205. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, Yang H, Rosner G, Verstovsek S et al. Phase 1/2 study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 2006; 108: 3271-3279.
206. Soriano AO, Yang H, Faderl S, Estrov Z, Giles F, Ravandi F et al. 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 2007; 110: 2302-2308.