Demethylating agents in myeloid malignancies

Current Opinion in Oncology

Volumn 20, Issue 6, 2008, Pages 705-710

  Garcia Manero, Guillermo ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

DNA methylation; Epigenetics; Leukemia

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ARYLBUTYRIC ACID DERIVATIVE; AZACITIDINE; CYTARABINE; DASATINIB; GEMTUZUMAB OZOGAMICIN; HISTONE DEACETYLASE INHIBITOR; LENALIDOMIDE; N (2 AMINOPHENYL) 4 [4 (3 PYRIDINYL) 2 PYRIMIDINYLAMINOMETHYL]BENZAMIDE; NILOTINIB; TRICHOSTATIN A; VALPROIC ACID;

ACUTE GRANULOCYTIC LEUKEMIA; BONE MARROW SUPPRESSION; BONE MARROW TUMOR; CANCER CHEMOTHERAPY; CANCER RISK; CANCER SURVIVAL; CLINICAL TRIAL; CONTINUOUS INFUSION; CONTROLLED CLINICAL TRIAL; DNA METHYLATION; GENE EXPRESSION; GENE SILENCING; HIGH RISK PATIENT; HUMAN; MYELODYSPLASTIC SYNDROME; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; REVIEW; UNITED STATES;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; AZACITIDINE; CLINICAL TRIALS AS TOPIC; DNA METHYLATION; EPIGENESIS, GENETIC; GENE SILENCING; HUMANS; LEUKEMIA; MYELODYSPLASTIC SYNDROMES; RISK; TREATMENT OUTCOME; VALPROIC ACID;

EID: 55749110754     PISSN: 10408746     EISSN: None     Source Type: Journal    
DOI: 10.1097/CCO.0b013e328313699c     Document Type: Review

References (37)

1. Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000; 1:11-19.
2. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128:683-692. This is an excellent state-of-the-art review on the epigenetics of cancer.
3. 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.
4. Kantarjian HM, O'Brien S, Cortes J, et al. Results of decitabine (5-aza-2′deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia. Cancer 2003; 98:522-528.
5. Fenaux P, Mufti G, Santini V, et al. Azacitidine treatment prolongs overall survival in higher risk MDS patients compared with conventional care regimens: results of the AZA-001 phase III study. Blood 2007; 110:250a. Although this is currently in abstract form, it is expected to be published by the end of the year. This is the first randomized study to show a significant effect on survival by any therapy MDS. Fundamental study in this field.
6. Yang AS, Doshi KD, Choi SW, et al. DNA methylation changes after 5-aza-2′-deoxycytidine therapy in patients with leukemia. Cancer Res 2006; 66:5495-5503.
7. Jabbour E, Issa JP, Garcia-Manero G, Kantarjian H. Evolution of decitabine development: accomplishments, ongoing investigations, and future strategies. Cancer 2008; 112:2341-2351.
8. Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980; 20:85-93.
9. Wijermans P, 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.
10. 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.
11. 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. This is a very important study summarizing the results with decitabine at MDACC and the basis for the 5-day schedule of this drug.
12. 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.
13. Kantarjian HM, O'Brien S, Huang X, et al. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer 2007; 109:1133-1137.
14. 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; 110:42a.
15. Steensma D, Baer M, Slack J, et al. Preliminary results of a phase II study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndrome. Blood 2007; 110:434a.
16. Issa JP, Kantarjian HM, Kirkpatrick P. Azacitidine. Nat Rev Drug Discov 2005; 4:275-276.
17. Choi SH, Byun HM, Kwan JM, et al. Hydroxycarbamide in combination with azacitidine or decitabine is antagonistic on DNA methylation inhibition. Br J Haematol 2007; 138:616-623.
18. 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.
19. 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.
20. Garcia-Manero G, Issa JP. Histone deacetylase inhibitors: a review of their clinical status as antineoplastic agents. Cancer Invest 2005; 23: 635-642.
21. Gottlicher M, Minucci S, Zhu P, et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 2001; 20:6969-6978.
22. Phiel CJ, Zhang F, Huang EY, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 2001; 276:36734-36741.
23. Davis R, Peters DH, McTavish D. Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1994; 47:332-372.
24. Kuendgen A, Strupp C, Aivado M, et al. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 2004; 104:1266-1269.
25. 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.
26. 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. This article is a classic example of combination epigenetic therapy in AML/ MDS.
27. 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.
28. Silverman L, McKenzie DR, Peterson BL, et al. Response rates using international working group (IWG) criteria in patients with myelodysplastic syndrome treated with azacytidine. Blood 2005; 106:709a.
29. Yang H, Hoshino K, Sanchez-Gonzalez B, et al. Antileukemia activity of the combination of 5-aza-2′-deoxycytidine with valproic acid. Leuk Res 2005; 29:739-748.
30. Garcia-Manero G, Yang A, Klimek V, et al. Phase I/II study of MGCD0103, an oral isotype-selective histone deacetylase (HDAC) inhibitor, in combination with 5-azacitidine in higher-risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Blood 2007; 110:137a.
31. Garcia-Manero G, Assouline S, Cortes J, et al. Phase I study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia. Blood 2008; 15:981-989.
32. Sekeres M, List A, Cuthbertson D, et al. Preliminary Results from a Phase I Study of Revlimid® (Lenalidomide) in Combination with Vidaza® (Azacitidine) in Patients with Advanced Myelodysplastic Syndromes (MDS). Blood 2007; 110:437a.
33. Holsinger A, Ramakrishnan A, Storer B, et al. Therapy of myelodysplastic syndrome (MDS) with azacitidine given in combination with etanercept: a phase II study. Blood 2007; 110:435a.
34. Nand S, Godwin J, Smith S, et al. Azacitidine plus gemtuzumab ozogamicin (GO): a novel combination in the treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) in the elderly. Blood 2007; 110:589a.
35. Oki Y, Kantarjian HM, Gharibyan V, et al. Phase II study of low-dose decitabine in combination with imatinib mesylate in patients with accelerated or myeloid blastic phase of chronic myelogenous leukemia Cancer 2007; 109:899-906.
36. Qrövdal 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.
37. Garcia-Manero G, Stoltz M, Ward M, et al. A pilot pharmacokinetic study of oral azacitidine. Leukemia 2008; 22:1680-1684.