title: Mutations in epigenetic modifiers in acute myeloid leukemia and their clinical utility.
abstract: Recent studies have identified recurrent mutations in genes that encode proteins crucial in the epigenetic regulation of gene transcription in hematologic malignancies. Somatic mutations in epigenetic modifiers, including IDH1, IDH2, TET2, DNAMT3A, ASXL1, MLL and EZH2 are enriched in patients with acute myeloid leukemia (AML), especially those with intermediate-risk cytogenetics. Here we describe the clinic-biologic features of AML patients with these mutations, their prognostic relevance and potential as therapeutic targets. The epigenetic alterations are present as the early pre-leukemic events and usually remain stable during disease evolution, implying the potential to be biomarkers for minimal residual disease monitoring. The high frequency of mutations in epigenetic modifiers and their prognostic implications shed light on the development of epigenetic therapy.
authors.affiliation: a Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital , National Taiwan University , Taipei , Taiwan.
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Hou
authors.affiliation: a Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital , National Taiwan University , Taipei , Taiwan.
authors.forename: Hwei-Fang
authors.initials: HF
authors.lastname: Tien
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006657:Histones; D011518:Proto-Oncogene Proteins; D007521:Isocitrate Dehydrogenase; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: Acute myeloid leukemia; epigenetic modifiers; epigenetic therapy; leukemogenesis; mutation; prognosis