Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome

Br J Cancer. 2006 Jan 30;94(2):323-32. doi: 10.1038/sj.bjc.6602939.


We report the isolation of the 5' flanking region of GRAF (GTPase regulator associated with the focal adhesion kinase), previously described as a putative tumour suppressor gene of acute myelogenous leukaemia and myelodysplastic syndrome, and demonstrate its promoter activity in reporter gene assays. Two putative protein-binding sites are identified of which one was sensitive to CpG methylation. The suppressed GRAF expression could be restored in leukaemia cell lines by treatment with a demethylating agent and an inhibitor of histone deacetylases. In contrast to normal tissues, which tested negative for GRAF promoter methylation, 11 of 29 (38%) bone marrow samples from patients with acute myeloid leukaemia or myelodysplastic syndrome were positive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Base Sequence
  • Child
  • GTPase-Activating Proteins / genetics*
  • Humans
  • K562 Cells
  • Leukemia, Myeloid / genetics*
  • Methylation
  • Molecular Sequence Data
  • Myelodysplastic Syndromes / genetics*
  • Promoter Regions, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction


  • ARHGAP26 protein, human
  • GTPase-Activating Proteins