Methylation of DAPK1 promoter: frequent but not an adverse prognostic factor in myelodysplastic syndrome.

Promoter hypermethylation plays an important role in the inactivation of cancer-related genes. This abnormality occurs early in leukemogenesis and seems to be associated with poor prognosis in myelodsplastic syndrome (MDS). The identification of more inactivated tumor suppressor genes contributing to the development of MDS may lead to further elucidation of the biology of this disease and help to identify novel targets for therapy. In this study, the methylation status of death-associated protein kinase 1 (DAPK1) gene promoter was analyzed by using methylation-specific polymerase chain reaction in bone marrow (BM) samples from 59 patients with different stages of MDS. The abnormal methylation of the DAPK1 gene was found in 37 of 59 (62.7%) MDS cases. The correlation was significant between the sex and the methylation status of DAPK1 promoter in MDS patients (R=0.332, P=0.010). Furthermore, methylation status of DAPK1 promoter was associated with the percentage of BM blasts (R=0.346, P=0.010) and International Prognosis Scoring System (IPSS) groups (R=0.278, P=0.034). The estimated 50% survival time of the methylated DAPK1 group and unmethylated group was 20 and 33 months, respectively. There was no significant difference between these two groups (chi2=0.652, P=0.419). Multivariate analysis identified the age older than 50 years, the Int-2/high-risk categories of IPSS and the advanced stage MDS (RAEB-1/RAEB-2) in WHO classification as negative prognostic factors (P<0.05). Aberrant methylation of DAPK1 gene promoter had no influence on the prognosis of MDS despite of its increasing occurrence during disease progression.