Induction of apoptosis in CD4+ prolymphocytic leukemia by deoxyadenosine and 2′-deoxycoformycin

Abstract The leukemic cells of a patient with CD4 + prolymphocytic leukemia were treated in vitro with 5 μM deoxyadenosine and 60 μM2′-deoxycoformycin (dCF), an inhibitor of adenosine deaminase (ADA). Following treatment, the leukemic cell dATP level increased to 378 pmol/10 6 cells on day 3, after which the level plateaued. Apoptosis was apparent following 4 h of incubation, and by day 8 34% of the chromatin was fragmented. Apoptosis also occurred in control cells, but to a lesser extent than in drug-treated cells. When the patient was treated with dCF, 4 mg/M 2 i.v. the leukemic cell ADA activity was inhibited 24 h following treatment, and the lymphocyte dATP content increased to 303 pmol/10 6 cells by day 6. The lymphocyte count fell 60% in 1 week, but during this time there was no evidence of apoptosis in these cells. Thus, if dCF induces apoptosis in vivo , the effete cells may be rapidly cleared from the circulation and thus elude detection.