title: Abnormal methylation of GRAF promoter Chinese patients with acute myeloid leukemia.
abstract: The epigenetic disturbances are recognized as an alternative mechanism contributing to the pathogenesis of acute myeloid leukemia (AML). GTPase regulator associated with focal adhesion kinase (GRAF), a putative tumor suppressor gene, was revealed with mutations and promoter methylation in AML and myelodysplastic syndrome. In this study, we investigated the methylation status of GRAF promoter in Chinese AML patients. Aberrant methylation of GRAF promoter was detected in 66.7% (88/132) of the cases analyzed. The methylation of GRAF gene could be detected in all FAB subtypes and in all cytogenetic risk groups. There were no significant differences in clinical features, FAB subtypes and cytogenetic risk groups between patients with and without GRAF methylation. GRAF transcript was significantly lower in AML group compared to controls (3.30 vs 56.06, P<0.001). Both patients with methylated GRAF gene and those without methylated GRAF gene had significantly lower GRAF transcript than controls (P<0.001). Furthermore, GRAF transcript was significantly lower in patients with methylated GRAF than those without methylated GRAF (1.64 vs 6.42, P=0.005). These findings suggest that the hypermethylation of GRAF promoter might be one of early events in the development of AML.
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Zhen
authors.initials: Z
authors.lastname: Qian
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.forename: Dong-ming
authors.initials: DM
authors.lastname: Yao
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Run-bi
authors.initials: RB
authors.lastname: Ji
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Gao-fei
authors.initials: GF
authors.lastname: Xiao
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D019175:DNA Methylation; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C115971:ARHGAP26 protein, human; D020690:GTPase-Activating Proteins