Selective toxicity of deoxyguanosine and arabinosyl guanine for T- leukemic cells

Abstract

Deoxyguanosine is selectively cytotoxic to leukemic cells from patients with T-acute lymphoblastic leukemia (T-ALL), whereas all other leukemic cell types were significantly less sensitive. Arabinosylguanine, a deoxyguanosine analog resistant to cleavage by purine nucleoside phosphorylase, is a more potent inhibitor of DNA synthesis in T- leukemic cells than deoxyguanosine and retains a selective cytotoxic activity for T-leukemic cells. Deoxyguanosine and arabinosylguanine are phosphorylated to deoxyGTP and arabinosylGTP, respectively, by T cells but not by other cell types. The phosphorylation and the cytotoxicity of arabinosylguanine are prevented by deoxycytidine. The selectivity of arabinosylguanine for malignant T cells, the exquisite sensitivity of these cells to the drug, and the failure of PNP to cleave the nucleoside indicate its potential in the treatment of T-ALL.