title: Epigenetic regulators and their impact on therapy in acute myeloid leukemia.
abstract: Genomic studies of hematologic malignancies have identified a spectrum of recurrent somatic alterations that contribute to acute myeloid leukemia initiation and maintenance, and which confer sensitivities to molecularly targeted therapies. The majority of these genetic events are small, site-specific alterations in DNA sequence. In more than two thirds of patients with de novo acute myeloid leukemia mutations epigenetic modifiers are detected. Epigenetic modifiers encompass a large group of proteins that modify DNA at cytosine residues or cause post-translational histone modifications such as methylations or acetylations. Altered functions of these epigenetic modifiers disturb the physiological balance between gene activation and gene repression and contribute to aberrant gene expression regulation found in acute myeloid leukemia. This review provides an overview of the epigenetic modifiers mutated in acute myeloid leukemia, their clinical relevance and how a deeper understanding of their biological function has led to the discovery of new specific targets, some of which are currently tested in mechanism-based clinical trials.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center.
authors.forename: Friederike
authors.initials: F
authors.lastname: Pastore
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA leviner@mskcc.org.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008745:Methylation / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000964:Antimetabolites, Antineoplastic; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D006657:Histones; D009363:Neoplasm Proteins