INDUCTION OF APOPTOSIS BY CHLORODEOXYADENOSINE AND DEXAMETHASONE IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA

Apoptosis, programmed cell death, occurs in a variety of cellular syst ems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia (B-CLL). Lymphocytes of 29 untreated patients and 9 healthy controls were isolated and incubated for 24 hours in the pr esence or absence of either Dex (2 mu M) (n = 15) or 2-CdA (3 mu M) (n = 14). Following incubation the cells were harvested and their DNA ex tracted and analysed for internucleosomal DNA cleavage by UV illuminat ion after electrophoresis on agarose slab gel containing ethidium brom ide. In the Dex group, 10 patients showed dexamethasone independent sp ontaneous apoptosis appearing 24 hours after the start of incubation. These were the only instances of dexamethasone-enhanced apoptosis. Fiv e patients showed no spontaneous or dexamethasone induced apoptosis. O f the 2-CdA group, 5 showed spontaneous apoptosis enhanced by 2-CdA. N o spontaneous apoptosis was observed in the cells from 9 other patient s, however, 2-CdA induced apoptosis in 8 cases in this group. This stu dy shows that monitoring of apoptosis in CLL may provide important inf ormation regarding susceptibility of the cells to drug induced apoptos is.