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.
Koski
T
T
Departments of Clinical Chemistry and Pathology, Tampere University Hospital and University of Tampere Medical School, P.O. Box 2000, FIN-33521, Tampere, Finland.
Aine
R
R
Vilpo
L
L
Vilpo
J
J
D000368:Aged; D016923:Cell Death / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D016572:Cyclosporine