Interleukin-2 prevents programmed cell death in chronic lymphocytic leukemia cells.
When B-cell chronic lymphocytic leukemia (B-CLL) cells derived from peripheral blood are cultured in vitro, a substantial proportion die spontaneously by programmed cell death (PCD). In this study, we reexamined this phenomenon with both B-CLL and T-CLL cells, using a serum-free culture system. After 48 h of culture, in B-CLL cells, 23.3% +/- 6.7% (mean +/- S.E.M., n = 3) of total DNA was fragmented, while in 2 cases of T-CLL, this value was 32% and 45%, respectively. Analysis by electrophoresis indicated that the DNA of the B-CLL and T-CLL cells had been cleaved into regular oligonucleosome fragments comprising approximately 180-200 base pairs. This process was significantly promoted by methylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in at least some cases. Since B-CLL and T-CLL cells often possess interleukin-2 (IL-2) receptors on their cell membranes, we assessed the effects of IL-2 on spontaneous PCD. After a 48-h culture PCD was inhibited by 100 units/ml IL-2 by 31.7% +/- 6.6% in B-CLL (n = 3) and by 47% in one of 2 cases of T-CLL. This protective effect of IL-2 against spontaneous PCD was dose- and time-dependent. These findings suggest that the viability of B-CLL and T-CLL cells in vivo is regulated both positively and negatively by intrinsic IL-2, glucocorticoids, and regulators of PKA activity. This process of cell death may be involved in the development of CLL.
Huang
R W
RW
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Tsuda
H
H
Takatsuki
K
K
D000368:Aged; D017209:Apoptosis; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D015461:Leukemia, Prolymphocytic, T-Cell / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000473:pathology
D007376:Interleukin-2