PURINE NUCLEOTIDE-METABOLISM - SPECIFIC ASPECTS IN CHRONIC LYMPHOCYTIC-LEUKEMIA LYMPHOCYTES

The metabolism of purine nucleotides was studied in human peripheral b lood lymphocytes from healthy subjects and patients with B-cell chroni c lymphocytic leukemia. Nucleotide content was determined by HPLC. The rate of de novo synthesis of purine nucleotides was measured kinetica lly by following the incorporation of C-14-formate into the nucleotide s of a lymphocyte suspension. The patterns of the main enzymes involve d in purine nucleotide metabolism (those of the salvage pathway and ca tabolism) were estimated by a radiochemical method. Although the data expressed in relation to cells and protein showed some discrepancies, several common differences were evident in both cases. The main differ ences were an increase in NAD and IMP, a sharp decrease in 5'-nucleoti dase activities and in total guanylate content and synthesis, and an i ncrease in the A/G ratio in lymphocytes of patients with respect to co ntrols. The changes in these parameters in CLL indicate an imbalance i n purine metabolism and may play a specific role in the biology of the leukemia cell. They are also potential biochemical markers of lymphoi d malignancies and may be useful in chemotherapic applications. (C) 19 97 Elsevier Science B.V.