Evidence against a direct cytotoxic effect of alpha interferon and zidovudine in HTLV-I associated adult T cell leukemia/lymphoma

The combination of the anti-viral agents, zidovudine (AZT) and interferon-c u (IFN), is a potent treatment of HTLV-I-associated adult T cell leukemia/l ymphoma (ATL). In this study we investigate the possible mechanism of actio n of this combination by examining several cellular parameters including ce ll proliferation, cell cycle distribution and apoptosis. The ATL-derived T cell lines HuT-102 and MT-2 served as models. HTLV-I negative T cell lines (CEM and Jurkat) were used as controls. No significant modification of cell growth was observed except at supra pharmacological doses of AZT and IFN. Moreover, these effects were less pronounced in HTLV-l-infected cell lines compared to control cell lines. AZT and IFN treatment did not induce any si gnificant modification of the expression of bcl-2 and p53. Interestingly no in vitro cytotoxic effect of AZT/IFN combination was observed on fresh leu kemic cells derived from an acute ATL patient at diagnosis despite achievem ent of in vivo complete remission using the same therapy. These results sug gest that the therapeutic effect of AZT and IFN is not through a direct cyt otoxic effect of these drugs on the leukemic cells.