title: Characterisation of the GRAF gene promoter and its methylation in patients with acute myeloid leukaemia and myelodysplastic syndrome.
abstract: 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.
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: S E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: O
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: A
authors.initials: A
authors.lastname: Weinhäusl
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: H
authors.initials: H
authors.lastname: Mettal
authors.forename: R M
authors.initials: RM
authors.lastname: Bohle
authors.forename: A
authors.initials: A
authors.lastname: Borkhardt
authors.forename: U
authors.initials: U
authors.lastname: Fuchs
mesh_terms: D000208:Acute Disease; D001483:Base Sequence; D002648:Child; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C115971:ARHGAP26 protein, human; D020690:GTPase-Activating Proteins