BIOCHEMICAL AND CLINICAL STUDIES OF CHRONIC LYMPHOCYTIC-LEUKEMIA

Attempts were made to identify biochemical parameters that would characterize leukemic cells obtained from patients with chronic lymphocytic leukemia at early stages of the disease and with more aggressive phases. These studies included (a) the quantitative estimation of the ribonucleotide pool and of the ability of the cells to utilize de novo vs salvage metabolites; and (b) the measurement of the extent of metabolic activation of selected antimetabolits such as ara-C and 6-MP. Cells obtained from the peripheral blood of six male patients with chronic lymphocytic leukemia were shown to possess a reduced ability to utilize de novo pathways of purine and pyrimidine biosynthesis as indicated by the lack of ATP and UTP formation from glycine and orotic acid, respectively. In one of these patients, however, although the cells initially lacked the ability of utilizing glycine and orotate, a progressive increase in TdR and glycine incorporation into nucleic acid was observed, and was found to reach a plateau within two months prior to death. In another patient, the ability of cells to utilize glycine for the formation of ATP was found to be coincident with the appearance of advanced and aggressive disease. Concurrent with these shifts from total reliance of cells on salvage pathways for nucleic acid synthesis, to at least partial dependence on de novo pathways, a change in the ribonucleotide profile was observed with a shift from lower to higher ATP/IMP ratios. In the four other patients studied, the clinical and the biochemical profiles were both stable and unchanged to date. © 1978.