Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo.
We have treated a patient with refractory T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin, a potent inhibitor of the enzyme adenosine deaminase. Inhibition of adenosine deaminase activity resulted in (1) an abrupt rise in plasma deoxyadenosine, but not adenosine, concentrations; (2) accumulation of deoxyadenosine triphosphate by lymphoblasts; (3) inhibition of the enzyme S-adenoylhomocysteine hydrolase; and (4) rapid lysis of the leukemic cells. The patient died suddenly 3 days after therapy was discontinued, and postmortem examination revealed a complete absence of leukemic cells in all organs. Pharmacologic inhibition of adenosine deaminase activity can result in the lysis of T lymphoblasts in vivo, and this effect appears to be mediated by deoxyadenosine.
D000241:Adenosine / Q000097:blood; D000293:Adolescent; D002470:Cell Survival / Q000187:drug effects; D003070:Coformycin / Q000494:pharmacology / Q000627:therapeutic use; D003839:Deoxyadenosines / Q000097:blood; D004791:Enzyme Inhibitors; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology
D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D003070:Coformycin; D000241:Adenosine