Deletion of the p16(INK4A) gene in ex vivo acute adult T cell lymphoma/leukemia cells and methylation of the p16(INK4A) promoter in HTLV type I-infected T cell lines

The stoichiometry of the p16(INK4A) and p15(INK4B) proteins bound to the cy clin D-CDK4/6 complex regulates the entry of cells into the G(1) phase of t he cell cycle. Thus, their level of expression is essential in maintaining regulated cell growth. In several tumors, deletion of these genes has been reported and, more recently, promoter methylation has been suggested as an alternative mechanism to decrease the expression of these cell cycle inhibi tor proteins. Here, we studied the methylation status and the integrity of the p16(INK4A) and p15(INK4B) genes in 8 chronically HTLV-I-infected T cell lines and in ex vivo cells from 14 ATLL patients. Deletion of the locus ca rrying both genes was not found in the HTLV-I-infected T cell lines but was found in seven of eight acute ATLL cases and in none of the PBMCs from the chronic cases or the affected lymph nodes of the lymphoma type. In contras t, partial or complete methylation of one or both genes was found only in c hronically HTLV-I T cells, Thus, HTLV-I infection targets the p16(INK4A) an d p15(INK4B) loci both in vitro and in vivo, although the mechanisms may di ffer.