Cyclosporin A-induced cell kill in vitro in various clinical-hematological types of B-cell chronic lymphocytic leukemia.

We investigated whether a known T cell modulator, Cyclosporin A (CyA) is also toxic to chronic lymphocytic leukemia (B-CLL), in vitro. In contrast to seven other drugs and two types of irradiation the dose-response curves for CyA were very steep among the 36 CLL patients investigated, and the intraindividual variation of ID(80) values was remarkably lower. The mode of CyA-induced cell death was 'apoptotic-like' as indicated by flow cytometric analysis, revealing cell condensation and annexin positivity. The partially smeary DNA fragmentation pattern together with the relatively slow process of cell death revealed a distinctive pattern of cell death in CLL. Leukemia cells from patients at an advanced clinical stage, of a diffuse histologic type and showing fast progression were the most sensitive to CyA. These new observations may have therapeutic implications in CLL.