title: The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome.
abstract: Over the past few years, large-scale genomic studies of patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have unveiled recurrent somatic mutations in genes involved in epigenetic regulation (DNMT3A, IDH1/2, TET2, ASXL1, EZH2 and MLL) and the spliceosomal machinery (SF3B1, U2AF1, SRSF2, ZRSR2, SF3A1, PRPF40B, U2AF2, and SF1). The identification of these mutations and their impact on prognostication has led to improvements in risk-stratification strategies and has also provided new potential targets for the treatment of these myeloid malignancies. In this review, we discuss the most recently identified genetic abnormalities described in MDS and AML and appraise the current status quo of the dynamics of acquisition of mutant alleles in the pathogenesis of AML, during the transformation from MDS to AML, and in the context of relapse after conventional chemotherapy.
  
  
  CONCLUSIONS
  Identification of somatic mutations in AML and MDS suggests new targets for therapeutic development.
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 428, Houston, TX 77030, USA. aquintas@mdanderson.org
authors: Connie A
authors: CA
authors: Larsson
authors: Gilbert
authors: G
authors: Cote
authors: Alfonso
authors: A
authors: Quintás-Cardama
mesh_terms: D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016158:Genes, p53; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D017381:Spliceosomes / Q000235:genetics
chemical_list: D002843:Chromatin
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