Aberrant methylation of GTPase regulator associated with the focal adhesion kinase (GRAF) promoter is an adverse prognostic factor in myelodysplastic syndrome

To the Editor: DNA hypermethylation of promoter region of tumor suppressor genes (TSGs) is now recognized as an important mechanism contributing to the malignant phenotype of myelodysplastic syndrome (MDS) (1). GTPase regulator associated with focal adhesion kinase (GRAF), located at chromosome 5q31 and its protein is ubiquitously expressed in various tissues (2), negatively regulates the small GTP-binding protein RhoA, which is well known for its growth-promoting effect in RAS-mediated malignant transformation (3, 4). Mutations and deletions of GRAF gene were found in some cases with acute myeloid leukemia (AML) or MDS with a deletion 5q (2). Furthermore, Bojesen et al. (5) found that GRAF gene promoter was methylated in 38% cases with AML and MDS. However, the impact of methylation of GRAF gene promoter on the prognosis of patients with AML and MDS has not yet been studied. In the present study, we aimed to detect the methylation status of GRAF promoter using the methylationspecific PCR assay (5) in the mononuclear cells from 68 primary MDS cases. The diagnosis and classification of MDS was based on the FAB and WHO criteria (6). The clinical features of 68 primary MDS cases studied were listed in Table 1. BM samples, collected from three donors of bone marrow transplantation, 12 patients with iron deficiency anemia, and five with idiopathic thrombocytopenic purpura, were used as controls.