Abstract
Death‐associated protein (DAP) kinase is a pro‐apoptotic serine/threonine kinase with a death domain, which is involved in apoptosis induced by interferon‐γ, tumor necrosis factor‐α, and Fas ligand. Down‐regulation of DAP kinase gene expression by hypermethylation of its promoter region might result in resistance to apoptotic cell death, and could provide a basis for tumor development. In the present study, we employed methylation‐specific polymerase chain reaction to examine the methylation status of CpG islands in the DAP kinase gene in 19 cases of T‐cell malignancies (including eight adult T‐cell leukemia/lymphoma), 24 of natural killer (NK)/T‐cell, and 34 of B‐cell. Frequency of methylation was significantly higher in B‐cell (27 of 34, 79.4%) than in T‐cell malignancies (nine of 19, 47.4%) (P<0.05). Fifteen of 24 (62.5%) NK/T‐cell lymphomas showed DNA methylation. One B‐cell lymphoma cell line with DNA methylation was resistant to apoptotic stimuli, and treatment of the cells with a demethylating agent restored apoptotic cell death. These findings suggested that suppression of DAP kinase expression by DNA methylation might play a substantial role in the development of not only B‐cell, but also T‐ and NK/T‐cell lymphomas. (Cancer Sci 2003; 94: 87–91)
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