Induction of apoptosis in CD4+ prolymphocytic leukemia by deoxyadenosine and 2'-deoxycoformycin.
The leukemic cells of a patient with CD4+ prolymphocytic leukemia were treated in vitro with 5 microM deoxyadenosine and 60 microM 2'-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/M2 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.
Johnston
J B
JB
Manitoba Institute of Cell Biology, Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
Lee
K
K
Verburg
L
L
Blondal
J
J
Mowat
M R
MR
Israels
L G
LG
Begleiter
A
A
D058892:Adenosine Deaminase Inhibitors; D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism*; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015463:Leukemia, Prolymphocytic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015649:Pentostatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D058892:Adenosine Deaminase Inhibitors; D015704:CD4 Antigens; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D015649:Pentostatin