title: Clinical development of demethylating agents in hematology.
abstract: The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine.
authors.forename: Shyamala C
authors.initials: SC
authors.lastname: Navada
authors.forename: Juliane
authors.initials: J
authors.lastname: Steinmann
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Silverman
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002986:Clinical Trials as Topic; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D000077209:Decitabine; D044127:Epigenesis, Genetic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D020125:Mutation, Missense; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; C000717967:DNMT3A protein, human; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D001374:Azacitidine