2-Chlorodeoxyadenosine: hairy cell leukemia takes a surprising turn.
2-Chlorodeoxyadenosine (2CdA; Cladribine; Leustatin) was developed as a result of the discovery that the death of lymphocytes in hereditary adenosine deaminase deficiency was the result of the accumulation of deoxynucleotides, specifically in lymphocytes, because of their unique enzymatic profile. This deoxyadenosine analog was selected from 25 candidate compounds because it was resistant to deamination by ADA and because it had a favorable therapeutic index. The lymphoid specific action of this drug is a function of the high deoxycytidine kinase and low 5' nucleotidase activity of lymphocytes. The drug appears to trigger apoptosis, very likely by preventing the repair of nicks in double-stranded DNA. Accordingly, 2-CdA has been found effective against a variety of lymphoid neoplasms. Hairy cell leukemia has proved to be most sensitive to its action, with approximately 80% of patients achieving a complete, long-lasting remission after a single five- or seven-day infusion. 2-CdA also shows promise in the treatment of autoimmune disorders.
Beutler
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Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Carson
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DA
D015762:2-Chloroadenosine / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy*
D015762:2-Chloroadenosine