The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome

Mol Cancer Res. 2013 Aug;11(8):815-27. doi: 10.1158/1541-7786.MCR-12-0695. Epub 2013 May 3.


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.

Implications: Identification of somatic mutations in AML and MDS suggests new targets for therapeutic development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic
  • Chromatin / genetics
  • DNA Methylation
  • Epigenesis, Genetic
  • Genes, p53
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Mutation*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Neoplasm Recurrence, Local
  • Spliceosomes / genetics


  • Chromatin