Purine nucleotide biosynthesis in leukemic promyelocytes treated with retinoid

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Purine nucleotide synthesis and the related enzyme activities during cell differentiation were examined in leukemic promyelocytes taken from a patient with acute promyelocytic leukemia (APL) being treated with retinol palmitate and in promyelocytic cell line HL- 60cells treated with retinol. In the patient with APL, treatment with retinol palmitate induced morphological and functional maturation of leukemic promyelocytes <I>in vivo</I>. Also in suspension cultures, retinol, the main metabolite of retinol palmitate in human plasma, induced morphological and functional maturation of HL- 60 cells. In these two types of cells, incorporation of hypoxanthine and glycine into the intracellular nucleotide pool decreased significantly. Both treated cells showed significantly increased hypoxanthine-guanine phosphoribosyltransferase activity, but decreased phosphoribosyl pyrophosphate synthetase activity. These findings suggest that the differentiated promyelocytic cells induced by retinol palmitate or retinol show a decrease in purine nucleotide synthesis and that the effect of conventional combination chemotherapy for APL, including 6 -mercaptopurine, may be reduced following treatment with retinol palmitate.