Use of hypomethylating agents in myelodysplastic syndromes.
Aberrant DNA methylation is one of the molecular hallmarks of cancer and leukemia. By repressing gene expression, it is considered a functional equivalent to the physical inactivation of tumor suppressor genes by deletions or mutations. To clinically exploit this process, compounds with DNA hypomethylating properties have been evaluated both in the laboratory and the clinic. Two such agents, 5-azacytidine and 5-aza-2'-deoxycytidine, are currently approved by the US Food and Drug Administration for the treatment of patients with myelodysplastic syndromes. Ongoing studies are evaluating alternative dosing schedules for these drugs and the activity and safety of this class of agent in combination with histone deacetylase inhibitors. Here we summarize the experience of hypomethylating agents in myelodysplastic syndromes.
Atallah
Ehab
E
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Garcia-Manero
Guillermo
G
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects*; D015254:DNA Modification Methylases / Q000187:drug effects*; D000077209:Decitabine; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
D000964:Antimetabolites, Antineoplastic; D056572:Histone Deacetylase Inhibitors; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine