Aberrantly Hypermethylated Genes in Adult T-Cell Leukemia Cells: The Implications in the Leukemogenesis.

Adult T-cell leukemia (ATL) is a highly aggressive neoplasm of helper T lymphocytes and is etiologically associated with human T-cell leukemia virus type I (HTLV-I). Although HTLV-I encoded Tax protein is thought to play a central role in the leukemogenesis of ATL, ATL cells frequently could not produce Tax protein by the somatic mutations, deletion and loss of 5′-LTR. Moreover, a long-term latent period (almost 60 years in Japan) precedes the onset of ATL, suggesting that multistep tumorigenesis is involved in development of ATL in addition to role of viral protein. Such transformation process is thought to include alterations of host genome: genetic and epigenetic changes. The epigenetic alteration, such as DNA methylation and histone modification, is commonly observed in various cancer cells. Recently, we reported that the aberrant expression of MEL1S gene, which is hypomethylated in ATL cells, confers resistance against transforming growth factor-beta.