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Knowledge of transformation associated differences in pyrimidine nucleotide metabolism of human leukemic cells, compared to healthy counterparts can be a rational basis for development of new antileukemic drugs. Peripheral blood cells of patients with acute lymphoblastic leukemia (ALL) contain increased amounts of guanine-, uracil- and cytosine- nucleotides and uridinediphosphate bound sugars with a changed composition. Moreover, the same deviations have also been found in the human ALL cell-line of T-lymphoblastic origin MOLT-3. Comparison of pyrimidine nucleotide synthesis from labeled precursors by MOLT-3 cells and growth-stimulated T-lymphocytes (TL’s), showed that CTP-synthetase ‘overactivity’ could cause the increase in cytosine nucleotides found in the malignant cell-line cells2. Uridine fluxes by pulse-chase experiments in living cells with emphasis on CTP-synthetase activity and differences herein between MOLT-3 cells, TL’s and differentiated resting MOLT-3 cells, were performed to get a better insight in the fluxes and the role of CTP-synthetase.

Recently, several reports have been published about abnormal purine and pyrimidine metabolism in leukemic cells as compared to normal peripheral blood cells. Enzyme activities1,2 as well as metabolite concentrations3,4 have been studied. These studies demonstrated marked differences in the activities of many enzymes controling purine and pyrimidine metabolism in leukemic cells, such as adenosine deaminase, purine nucleoside Phosphorylase and terminal deoxynucleotidyl transferase. De Abreu et al.3 determined significantly increased concentrations of adenine and uracil nucleotides in the lymphoblasts of patients with non-B, non-T acute lymphoblastic leukemia. Liebes et al.4 found increased concentrations of nicotinamide adenine nucelotides in lymphoid cells of patients with chronic lymphatic leukemia.

Abnormalities in purine and pyrimidine metabolism may be associated with cell-cycle phase, proliferation, immaturity or transformation. Therefore, detailed information concerning purine and pyrimidine pattern in malignant cells compared to normal cells is needed. Abnormal enzyme activities (1) as well as abnormal metabolite concentrations (2) have been described for leukemic cells.