Targeting Apoptosis Defects in Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin's lymphomas characterized by the clonal proliferation of skin-invasive mature T lymphocytes. Because of their low proliferative potential, the accumulation of clonal T cells is considered to be potentially due to their inability to undergo Fas-mediated apoptosis, a crucial process involved in T-cell homeostasis. Several reports have indicated a decrease in or absence of Fas expression in tumor cells in significant proportions of CTCL patients, whether or not associated with overexpression of apoptosis inhibitors. In this issue, Wu et al. confirm the impaired expression of Fas in CTCL cells. Moreover, they show that CTCL cells genetically engineered to re-express Fas acquire a sensitivity to FasL-induced apoptosis, opening new avenues for therapeutic intervention strategies in CTCL.