Biochemical changes induced in hairy-cell leukemia following treatment with the adenosine deaminase inhibitor 2'-deoxycoformycin.
The adenosine deaminase inhibitor 2'-deoxycoformycin and interferon are highly effective in the treatment of hairy-cell leukemia. In this study, a patient with type 2 hairy-cell leukemia was treated with one cycle of 2'-deoxycoformycin (4 mg/m2, i.v. weekly for 3 weeks), which was repeated at 9 wk. No toxicity was observed, and the hairy cell count fell from 72,000/mm3 to 5,000/mm3 in 3 mo, with a concomitant 50% decrease in the spleen size. The erythrocyte deoxyadenosine triphosphate content increased to 13.6 pmol/10(6) cells following the initial three weekly treatments, but there was no decrease in the adenosine triphosphate pool size and no evidence of hemolysis. The hairy cell adenosine deaminase activity was inhibited by greater than 95% 24 h following the first 2'-deoxycoformycin injection and returned to the pretreatment value at Day 8, although there was a linear decline in peripheral hairy cell count (50%) during this period. No ultrastructural changes were observed in the hairy cells following 2'-deoxycoformycin to suggest lymphocytotoxicity or cellular differentiation. The antitumor activity of 2'-deoxycoformycin could not be attributed to alterations in the hairy cell deoxyadenosine triphosphate/adenosine triphosphate levels or to the induction of DNA strand breaks. Additionally, the plasma levels of interferon did not change during therapy, making it unlikely that 2'-deoxycoformycin exerts its activity by inducing endogenous interferon synthesis.
J B
JB
Johnston
A
A
Begleiter
L
L
Pugh
M K
MK
Leith
J A
JA
Wilkins
D J
DJ
Cavers
L G
LG
Israels
D000241:Adenosine / Q000097:blood; D000243:Adenosine Deaminase / Q000032:analysis; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D004247:DNA; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003839:Deoxyadenosines / Q000097:blood; D006801:Humans; D007372:Interferons / Q000097:blood; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D003838:Deoxyadenine Nucleotides; D003839:Deoxyadenosines; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D000255:Adenosine Triphosphate; D004247:DNA; D007372:Interferons; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine; C026600:2'-deoxyadenosine triphosphate