Purine metabolism of lymphocytes. Targets for chemotherapy drug development.

The unique metabolic profile that renders lymphoid cells sensitive to purine deoxynucleosides also accounts for the response of chronic lymphoid malignancies to purine analogues. Consistent with earlier observations in children with adenosine deaminase deficiency, a profound and relatively selective lymphocyte depletion results from treatment with drugs that elevate or mimic deoxyadenosine. Three such agents available for clinical use are 2-chlorodeoxyadenosine, 2'-deoxycoformycin, and fludarabine phosphate. In addition to a review of the relevant biochemistry and cellular pharmacology of these agents in target lymphoid cells, this article reviews the current clinical response data in leukemias and lymphoma.