INDUCTION OF APOPTOSIS BY 2-CHLORODEOXYADENOSINE IN B-CELL CHRONIC LYMPHOCYTIC-LEUKEMIA

We investigated whether 2-chlorodexoyadenosine could induce apoptosis in B cell chronic lymphocytic leukemia (B-CLL) cells in vitro using cl inically achievable drug doses, measuring apoptosis ratio by flow cyto metry. B cells were isolated from previously untreated patients and ap optosis was measured in these cells immediately after isolation and fo llowing incubation in vitro, without and with 2-chlorodeoxyadenosine a t different concentrations, for 24 and 48 h. Distribution of cellular DNA content and quantitative analysis of apoptosis were determined by standard propidium iodide staining and flow cytometry. Spontaneous apo ptosis occurred in B-CLL cells incubated in vitro in the absence of dr ug, but the level of apoptosis was greater in cells treated with 2-chl orodeoxyadenosine after the second day of culture. The present in vitr o study of B-CLL cells from previously untreated patients suggests thi s chemotherapeutic agent activates a program of cell death by apoptosi s using a drug dose equivalent to the physiological concentration used in patients in vivo. These data reveal an interesting possibility in the 2-chlorodeoxyadenosine treatment of untreated patients by neoplast ic B cell apoptosis induction.