The rationale and use of hypomethylation agents in adult acute myeloid leukemia

Expert Opinion on Drug Discovery

Volumn 4, Issue 2, 2009, Pages 195-205

  Thomas, Xavier ^a   Chelghoum, Youcef ^a   Barraco, Fiorenza ^a   Troncy, Jacques ^a  

^a EDOUARD HERRIOT HOSPITAL   (France)

Author keywords

Acute myeloid leukemia; Chemotherapy; DNA methylation; DNA methyltransferases; Emerging drugs; Epigenetic; Histone deacetylases; Hypomethylating agents

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ARYLBUTYRIC ACID DERIVATIVE; AZACITIDINE; CYTARABINE; FLUCYTOSINE DEOXYRIBOSIDE; HISTONE DEACETYLASE INHIBITOR; HYDRALAZINE; METHYLTRANSFERASE INHIBITOR; MULTIDRUG RESISTANCE PROTEIN 1; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; PANOBINOSTAT; PROCAINAMIDE; PROCAINE; RNA; TRICHOSTATIN A; VALPROIC ACID; VORINOSTAT; ZEBULARINE;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; BONE MARROW SUPPRESSION; CANCER INHIBITION; CHROMATIN STRUCTURE; CPG ISLAND; DIARRHEA; DNA METHYLATION; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG USE; ELDERLY CARE; EPIGENETICS; FATIGUE; GENE EXPRESSION REGULATION; GENE SILENCING; HUMAN; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; NUCLEOSOME; PRIORITY JOURNAL; PROMOTER REGION; RASH; REVIEW; SIDE EFFECT; THROMBOCYTOPENIA; TRANSCRIPTION REGULATION; TUMOR SUPPRESSOR GENE; VOMITING; WEIGHT REDUCTION;

EID: 67649217253     PISSN: 17460441     EISSN: None     Source Type: Journal    
DOI: 10.1517/17460440802707337     Document Type: Review

References (87)

1. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 2003;21:4642-4649 (Pubitemid 46594039)
2. Fraga MF, Herranz M, Espada J, et al. A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res 2004;64:5527-5534 (Pubitemid 39095543)
3. Eden A, Gaudet F, Waghmare A, Jaenisch R. Chromosomal instability and tumors promoted by DNA hypomethylation. Science 2003;300:455 (Pubitemid 36444319)
4. Waddington CH. Preliminary notes on the development of the wings in normal and mutant strains of drosophila. Proc Nat Acad Sci USA 1939;25:299-307
5. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983;301:89-92 (Pubitemid 13154475)
6. Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000;1:11-19
7. Rice JC, Allis CD. Code of silence. Nature 2001;414:258-261 (Pubitemid 33097787)
8. Kouzarides T. Chromatin modifications and their function. Cell 2007;128:693-705 (Pubitemid 46273577)
9. Bjornsson HT, Fallin MD, Feinberg AP. An integrated epigenetic and genetic approach to common human disease. Trends Genet 2004;20:350-358 (Pubitemid 38943025)
10. Holliday R. The inheritance of epigenetic defects. Science 1987;238:163-170 (Pubitemid 17139717)
11. Herman JG, Baylin SB. Gene silencing in cancer in association with promotor hypermethylation. N Engl J Med 2003;349:2042-2054 (Pubitemid 37448928)
12. Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promotor DNA methylation in the human genome. Nat Genet 2007;39:457-466 (Pubitemid 46514772)
13. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Gen 2002;3:415-428 (Pubitemid 34587077)
14. Grady WM, Willis J, Guilford PJ, et al. Methylation of the CDH1 promotor as the second genetic hit in hereditary diffuse gastric cancer. Nat Genet 2000;26:16-17 (Pubitemid 30692848)
15. Brueckner B, Lyko F. DNA methyltransferase inhibitors: old and new drugs for an epigenetic cancer therapy. Trends Pharmacol Sci 2004;25:551-554 (Pubitemid 39371143)
16. Jenuwein T, Allis CD. Translating the histone code. Science 2001;293:1074-1080 (Pubitemid 32758077)
17. Hake SB, Xiao A, Allis CD. Linking the epigenetic 'language' of covalent histone modifications to cancer. Br J Cancer 2004;90:761-769
18. Berstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell 2007;128:669-681 (Pubitemid 46273573)
19. Karpf AR, Matsui S. Genetic disruption of cytosine DANN methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res 2005;65:8635-8639 (Pubitemid 41377349)
20. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human diseases and prospects for epigenetic therapy. Nature 2004;429:457-463 (Pubitemid 38715140)
21. Silverman LR, Demakos EP, Peterson BL, 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 (Pubitemid 34525728)
22. Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:52-57 (Pubitemid 46053042)
23. Rosenbauer F, Tenen DG. Transcription factors in myeloid development: balancing differentiation with transformation. Nat Rev Immunol 2007;7:105-117 (Pubitemid 46174858)
24. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007;128:683-692 (Pubitemid 46273572)
25. Esteller M. Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 2007;8:286-298 (Pubitemid 46439286)
26. Toyota M, Kopecky KJ, Toyota MO, et al. Methylation profiling in acute myeloid leukemia. Blood 2001;97:2823-2829
27. Leone G, Voso MT, Teofili L, Lubbert M. Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol 2003;109:89-102 (Pubitemid 37324746)
28. Boumber YA, Kondo Y, Chen X, et al. RIL, a LIM gene on 5q31, is silenced by methylation in cancer and sensitizes cancer cells to apoptosis. Cancer Res 2007;67:1997-2005 (Pubitemid 46424216)
29. Thomas X, Teillon MH, Belhabri A, et al. Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and during complete remission. Hemat Cell Ther 1999;41:19-26 (Pubitemid 29111280)
30. Esteller M. Epigenetics in cancer. N Engl J Med 2008;358:1148-1159
31. Quesnel B, Guillerm G, Vereecque R, et al. Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and acquiredduring disease progression. Blood 1998;91:2985-2990 (Pubitemid 28227550)
32. Brakensiek K, Langer F, Schlegelberger B, et al. Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome. Br J Haematol 2005;130:209-217 (Pubitemid 41602521)
33. Hopfer O, Komor M, Koehler IS, et al. DNA methylation profiling of myelodysplastic syndrome hematopoietic progenitor cells during in vitro lineage-specific differentiation. Exp Hematol 2007;35:712-723 (Pubitemid 46628726)
34. Ozdag H, Teschendorff AE, Ahmed AA, et al. Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics 2006;7:90 (Pubitemid 43852761)
35. Esteller M. Epigenetics provides a new generation of oncogenes and tumor-suppressor genes. Br J Cancer 2006;94:179-183 (Pubitemid 43151531)
36. Moe-Behrens GH, PandolfiPP. Targeting aberrant transcriptional repression in acute myeloid leukemia. Rev Clin Exp Hematol 2003;7:139-159
37. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006;6:38-51 (Pubitemid 43054973)
38. Melnick A. Predicting the effect of transcription therapy in hematologic malignancies. Leukemia 2005;19:1109-1117 (Pubitemid 40945991)
39. Erfurth F, Hemenway CS, De Erkenez AC, Domer PH. MLL fusion partners AF4 and AF9 interact at subnuclear foci. Leukemia 2004;18:92-102 (Pubitemid 38159444)
40. Zeisig BB, Milne T, Garcia-Cuellar MP, et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol 2004;24:617-628 (Pubitemid 38057914)
41. Johan MF, Bowen DT, Frew ME, et al. Aberrant methylation of the negative regulators RASSFIA, SHP-1 and SOCS-1 in myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol 2005;129:60-65 (Pubitemid 40524052)
42. Figueroa ME, Fandy T, McConnell MJ, et al. Myelodysplastic syndrome (MDS) displays profound and functionally significant epigenetic deregulation compared to acute myeloid leukemia (AML) and normal bone marrow cells. Blood 2007;110(Suppl 1):108a-109a
43. Issa JP, Garcia-Manero G, Giles FJ, 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 (Pubitemid 38268953)
44. Gore SD, Baylin S, Sugar E, et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006;66:6361-6369
45. Daskalakis M, Nguyen TT, Nguyen C, et al. Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-aza-2′-deoxycytidine (decitabine) treatment. Blood 2002;100:2957-2964
46. Pliml J, Sorm F. Synthesis of 2′-deoxy-D-ribofuranosyl-5- azacytosine. Coll Czech Chem Commun 1964;29:2576-2577
47. Sorm F, Vasely J. Effect of 5-aza-2′-deoxycytidine against leukemic and hematopoietic issues in AKR mice. Neoplasm 1968;15:339-343
48. Rivard GE, Momparler RL, Demers J, et al. Phase I study on 5-aza-2′-deoxycytidine in children with acute leukemia. Leukemia Res 1981;5:453-462 (Pubitemid 12252112)
49. 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 (Pubitemid 30134342)
50. Taylor SM. 5-aza-2′-deoxycytidine-cell differentiation and DNA methylation. Leukemia 1993;7(Suppl 1):3-8
51. Momparler RL, Samson J, Momparler LF, Rivard GE. Cell cycle effects and cellular pharmacology of 5-aza-2′-deoxycytidine. Cancer Chemother Pharmacol 1984;13:191-194 (Pubitemid 14048989)
52. Momparler RL, Goodman J. In vitro cytotoxic and biochemical effects of 5-aza-2′-deoxycytidine. Cancer Res 1977;37:1636-1639
53. Steensma DP, Baer MR, Slack JL, et al. Preliminary results of a phase II study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes (MDS). Blood 2007;110(Suppl 1):434a-435a
54. Wijermans PW, Lubbert M, Verhoef G, et al. 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
55. Wijermans PW, Lubbert M, Verhoef G, 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 elderly patients. J Clin Oncol 2000;18:956-962 (Pubitemid 30123770)
56. Lubbert M, Wijermans P, Kunzmann R, et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 2001;114:349-357 (Pubitemid 32762234)
57. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794-1803
58. Kantarjian H, Garcia-Manero G, O'Brien S, et al. Survival and efficacy of decitabine in myelodysplastic syndromes (MDS), analysis of the 5-day IV dosing regimen. Blood 2007;110(Suppl 1):42a
59. Cashen A, Schiller GJ, Larsen JS, et al. Phase II study of low-dose decitabine for the front-line treatment of older patients with acute myeloid leukemia (AML). Blood 2006;108(Suppl 1):561a-562a
60. Lubbert M, Ruter B, Schmid M, et al. Continued low-dose decitabine (DAC) is an active frist-line treatment of older AML patients: First results of a multicenter phase II study. Blood 2005;106(Suppl 1):527a
61. Ravandi F, Kantarjian H, Cohen A, et al. Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: results of a phase I study. Bone Marrow Transplant 2001;27:1221-1225 (Pubitemid 32655389)
62. Glover AB, Leyland-Jones B. Biochemistry of azacitidine: a review. Cancer Treat Rep 1987;71:959-964 (Pubitemid 17151374)
63. Murakami T, Li X, Gong J, et al. Induction of apoptosis by 5-azacytidine: drug concentration-dependent differences in cell cycle specificity. Cancer Res 1995;55:3093-3098
64. Charache S, Dover G, Smith K, et al. Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the t-d-b-globin gene complex. Proc Natl Acad Sci USA 1983;80:4842-4846
65. Silverman LR, Holland JF, Weinberg RS, et al. Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia 1993;7:21-29 (Pubitemid 23184796)
66. Silverman LR, McKenzie DR, Peterson BL, 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 (Pubitemid 46630737)
67. Kornblith AB, Herndon JE, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol 2002;20:2441-2452 (Pubitemid 34525729)
68. Fenaux P, Mufti GJ, Santini V, et al. Azacitidine (AZA) treatment prolongs overall survival (OS) in higher-risk MDS patients compared with conventional care regimens (CCR): results of the AZA-001 phase III study. Blood 2007;110(Suppl 1):250a
69. Lyons RM, Cosgriff T, Modi S, et al. Results of the initial treatment phase of a study of three alternative dosing schudules of azacitidine (Vidaza) in patients with myelodysplastic syndrome (MDS). Blood 2007;110(Suppl 1):251a
70. Grovdal M, Khan R, Aggerholm A, et al. Maintenance treatment with azacytidine for patients with high risk myelodysplastic syndromes or acute myeloid leukaemia in complete remission after intensive chemotherapy. Blood 2007;110:251a
71. Graef T, Kuendgen A, Fenk R, et al. Successful treatment of relapsed AML after allogeneic stem cell transplantation with azacitidine. Leuk Res 2007;31:257-259 (Pubitemid 44854182)
72. Garcia-Manero G, Stolz ML, Ward MR, et al. A pilot pharmacokinetic study of oral azacitidine. Leukemia 2008;22:1680-1684
73. Robert MF, Morin S, Beaulieu N, et al. DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 2003;33:61-65 (Pubitemid 36068683)
74. Fang MZ, Wang Y, Ai N, et al. Tea polyphenol-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 2003;63:7563-7570 (Pubitemid 37466673)
75. Cheng JC, Matsen CB, Gonzales FA, et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst 2003;95:399-409 (Pubitemid 36395260)
76. Muller CI, 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 (Pubitemid 44524413)
77. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006;5:769-784 (Pubitemid 44348499)
78. Kuendgen A, Strupp C, Aivado M, et al. Treatment of myelodysplastic syndromes with valproic acid alone or in combination withall-trans retinoic acid. Blood 2004;104:1266-1269 (Pubitemid 39166498)
79. Gottlicher M, Minucci S, Zhu P, et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EBMO J 2001;20:6969-6978 (Pubitemid 34062289)
80. Cimino G, Lo Coco F, Fenu S, 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 (Pubitemid 44449209)
81. 2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors. J Med Chem 2004;47:467-474
82. Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioassays 1995;17:423-430
83. Bug G, Schwarz K, Schoch C, et al. Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia. Haematologica 2007;92:542-545 (Pubitemid 350144299)
84. Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999;21:103-107 (Pubitemid 29036293)
85. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, 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 (Pubitemid 44776863)
86. Blum W, Klisovic RB, Hackanson B, et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J Clin Oncol 2007;25:3884-3891 (Pubitemid 47477265)
87. Soriano AO, Yang H, Faderl S, 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 (Pubitemid 47523148)