Clinical and oncological significance of aberrant Fas (APO-1/CD95) isoform expression in adult T-cell leukemia

Fas (APO-1/CD95), a transmembrane death receptor mediating apoptosis, can induce cell deathin vivo andin vitro of not only normal T-cells but also leukemic T-cells. This indicates that dysfunction in T-cell apoptosis may influence the natural history of the T-cell neoplasms, such as adult T-cell leukemia (ATL) caused by the retrovirus HTLV-1. Fas is ubiquitous, and down-regulated or mutated Fas has been widely detected in tumor cells that escape from elimination via Fas-mediated apoptosis. De novo fresh ATL cells and cell lines derived from the de novo cells, however, express Fas abundantly on the cell surface and are susceptible to Fas ligand and agonistic agents. On the other hand, there are two types of Fas gene transcripts, full-length and alternatively splicing truncated forms corresponding to membrane and soluble Fas isoforms, respectively. Focusing on membrane and soluble Fas isoforms and ATL pathology mediated by apoptosis, this paper reviews and discusses our ATL cases and ATL cell lines, which provide useful "experiments of nature" for understanding the role of Fas-mediated apoptosis in tumor biology.