High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia

Blood. 2004 Mar 15;103(6):2316-24. doi: 10.1182/blood-2003-09-3074. Epub 2003 Nov 13.


A high incidence of somatically acquired point mutations in the AML1/RUNX1 gene has been reported in poorly differentiated acute myeloid leukemia (AML, M0) and in radiation-associated and therapy-related myelodysplastic syndrome (MDS) or AML. The vast majority of AML1 mutations identified in these diseases were localized in the amino (N)-terminal region, especially in the DNA-binding Runt homology domain. In this report, we show that AML1 point mutations were found in 26 (23.6%) of 110 patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt), and AML following MDS (defined these 3 disease categories as MDS/AML). Among them, 9 (8.2%) mutations occurred in the carboxy (C)-terminal region, which were exclusively found in MDS/AML and were strongly correlated with sporadic MDS/AML. All patients with MDS/AML with an AML1 mutation expressed wild-type AML1 protein and had a significantly worse prognosis than those without AML1 mutations. Most AML1 mutants lost trans-activation potential, regardless of their DNA binding potential. These data suggested that AML1 point mutation is one of the major driving forces of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • COS Cells
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • HeLa Cells
  • Humans
  • Incidence
  • Leukemia, Myeloid / epidemiology*
  • Leukemia, Myeloid / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myelodysplastic Syndromes / epidemiology*
  • Myelodysplastic Syndromes / genetics*
  • Point Mutation
  • Protein Binding / genetics
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Transcription Factor AP-2
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Transcription Factor AP-2
  • Transcription Factors