Decitabine in acute myeloid leukemia.
Standard induction chemotherapy, depending on patient tolerability, is at present the treatment of choice in patients with acute myeloid leukaemia (AML) under the age of 75 years. Since AML is a disease primarily of the elderly, a large proportion of patients do not receive this therapy; therefore, novel treatment modalities are warranted. In addition, younger patients with poor-risk cytogenetics often have unsatisfactory results with conventional chemotherapy, so novel treatment options would represent a significant advancement in the management of this disease. The encouraging results of low-dose schedules of demethylating agents in myelodysplastic syndromes (MDS) have stimulated interest in the use of these agents in patients with AML. The DNA methylator phenotype of MDS and AML offers a biological rationale for treating these patients with doses of demethylating agents which act by reverting the hypermethylated state to an unmethylated state rather than by "classic" cytotoxicity mechanisms typically associated with higher doses. However, many issues surrounding this therapy need to be unravelled, including the role of different target genes that may become demethylated, and the potential use of combination therapy of hypomethylating agents with other drugs. This review will provide a summary of epigenetic processes in AML and the role of the demethylating agent 5-aza-2'-deoxycytidine (decitabine; Dacogen, MGI Pharma, Inc, Bloomington, MN).
Lübbert
Michael
M
Department of Medicine, Division of Hematology/Oncology, University of Freiburg Medical Center, Freiburg, Germany. luebbert@mm11.ukl.uni-freiburg.de
Minden
Mark
M
D000208:Acute Disease; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality
D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine