Induction of "in vitro" apoptosis by fludarabine in freshly isolated B-chronic lymphocytic leukemia cells.

The cytotoxic effects and apoptosis (programmed cell death) induced by fludarabine (FLU), interleukin-2 (IL-2), interleukin-4 (IL-4), IL-2 plus IL-4, alpha-interferon (alpha-IFN), and mafosfamide were evaluated "in vitro" on freshly isolated B-cell chronic lymphocytic leukemia (B-CLL) cells. Cytotoxicity was evaluated according to the soluble tetrazolium/formazan assay. Treatment with mafosfamide, fludarabine, and IL-4 resulted in significant anti-tumor activity against all the freshly isolated samples. On the other hand, no significant cytotoxic activity was observed with alpha-IFN, IL-2, and the combination of IL-2 and IL-4. Apoptosis was evaluated by electrophoresis gel of DNA oligonucleosomal fragments and only FLU significantly activated apoptosis in all the samples. It appears that fludarabine is active against B-CLL cells acting by an direct cytotoxic effect and/or the induction of cell death by apoptosis.