Apoptosis and cutaneous T cell lymphoma

The most successful therapies in the treatment of cutaneous T cell lymphoma (CTCL), which include localized X-ray therapy, total skin electron beam therapy, total skin therapy with psoralen and UVA or other forms of UV light therapy, topical chemotherapy, and even topical steroids, all work by inducing T cell apoptosis. Yet, these same malignant T cells, which readily undergo apoptosis after these therapies, are far less likely to do so after therapy with systemic chemotherapeutic agents that are often curative in B cell lymphomas. Apoptosis in T cells is a normal phenotype in that only a small fraction of nonneoplastic T cells fail to undergo apoptosis. Although we still understand relatively little regarding the molecular biology of CTCL, it is clear that the neoplastic cell clone or clones that predominate in this disease have defects in normal apoptotic control mechanisms. These can be overridden in most cases by the strong proapoptotic signals triggered by ionizing radiation and other agents. Better understanding of the mechanisms by which the latter occurs should help us both improve our current therapies and devise new ones.