INTERLEUKIN-2 PREVENTS PROGRAMMED CELL-DEATH IN CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS

When B-cell chronic lymphocytic leukemia (B-CLL) cells derived from pe ripheral blood are cultured in vitro, a substantial proportion die spo ntaneously by programmed cell death (PCD). In this study, we reexamine d 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 elect rophoresis indicated that the DNA of the B-CLL and T-CLL cells had bee n cleaved into regular oligonucleosome fragments comprising approximat ely 180-200 base pairs. This process was significantly promoted by met hylprednisolone and the protein kinase A (PKA) activator Sp-cAMPS in a t least some cases. Since B-CLL and T-CLL cells often possess interleu kin-2 (IL-2) receptors on their cell membranes, we assessed the effect s of IL-2 on spontaneous PCD. After a 48-h culture PCD was inhibited b y 100 units/ml IL-2 by 31.7% +/- 6.6% in B-CLL (n = 3) and by 47% in o ne of 2 cases of T-CLL. This protective effect of IL-2 against spontan eous PCD was dose- and time-dependent. These findings suggest that the viability of B-CLL and T-CLL cells in vivo is regulated both positive ly and negatively by intrinsic IL-2, glucocorticoids, and regulators o f PKA activity. This process of cell death may be involved in the deve lopment of CLL.