Biochemical Abnormality of DNA Synthesis

Six patients with acute and chronic myeloid leukemia (AML and CML) showed a low incorporation of labeled DNA precursors into basophilic erythroblasts. Based on mitotic indices and the use of vincristine as a stathmokinetic tool, it was evident that brisk proliferation in this cell compartment took place. Mic rospectrophotometric determination of single-cell DNA content showed that a considerable fraction of the erythroid cells were in DNA synthesis without incorporating an exogeneously supplied DNA precursor. Following inhibition of the de novo synthesis of nucleoside tnphosphates, the cells showed capacity for precursor incorporation. It is suggested that a biochemical abnormality, which leads to a high intranuclear nucleoside tniphosphate pool, may inhibit nucleoside kinases and hence the utilization of labeled nucleosides, as well as diluting the labeled precursors. The defect should probably be considered to be a biochemical expression of “leukemicness” of the erythroid cells. The frequency of the phenomenon described here cannot be determined from the present study. The patients are part of a series of 44 patients who were studied with the purpose to investigate the effect of cytostatic treatment on the cell cycle of the leukemic cells. Many of the patients’ had so little erythropoiesis left that studies as those described here could not be carried out. Therefore, the reported frequency of 6/44 of the observed phenomenon is almost certainly an underestimate. Consequently, cytokinetic studies of erythropoiesis in CML and AML, using tracer techniques alone, must be evaluated with caution.