Aberrant methylation of death-associated protein kinase 1 CpG islands in myelodysplastic syndromes.

Death-associated protein kinase 1 (DAPK1), a proapoptotic serine/threonine kinase, is a candidate tumor suppressor gene. We studied the methylation status of the promoter region of the DAPK1 gene and the expression of the DAPK1 protein in 78 bone marrow samples from untreated patients with myelodysplastic syndrome (MDS) by PCR and Western blot analysis. Hypermethylation of DAPK1 was present in 42.3% (33 of 78) of MDS specimens and was significantly correlated with the loss of DAPK1 mRNA and protein expression (p < 0.01). There were no significant differences in methylation frequency among subgroup of MDS. DAPK1 hypermethylation in MDS was associated with the presence of cytogenetic abnormalities in the bone marrow at the time of the initial diagnosis. A higher frequency of DAPK1 hypermethylation was found in the unfavorable cytogenetic risk group (12 of 21 cases; 57.1%) compared to the favorable cytogenetic risk group (5 of 20 cases; 25.0%, p = 0.0368). These findings suggest that suppression of DAPK1 expression by DNA methylation may play a substantial role in the development of MDS.