Impaired Pentose Phosphate Shunt and Decreased Glycolytic Activity in Lymphocytes of Chronic Lymphocytic Leukemia. Metabolic Pathway . . . ?

The purpose of this study was to determine whether proportional alterations in the hexose monophosphate shunt or Embden-Meyerhof pathways of leukemic lymphocyte glycolysis might provide a biochemical explanation for excess glycogen stored in these neoplastic cells in addition to delineating a possible cause for the decreased glucose tolerance shown by a large number of patients with chronic lymphocytic leukemia (CLL). The experimental technic consisted of incubating leukemic lymphocytes separately in Krebs-bicarbonate buffer, and autologous and paired homologous normal plasma, along with glucose-1-¹⁴C. Normal, control lymphocytes were similarly handled except that corresponding leukemic plasma became the homologous substitute. Evolved ¹⁴CO₂, trapped by sodium hydroxide, and collective glycolytic intermediates, isolated by anion exchange chromatography, were assayed by scintillation spectrometry. Compared to normal lymphocytes, the leukemic cells not only consumed less total sugar but also metabolized proportionately less carbohydrate via the hexose monophosphate shunt pathway as indicated by the diminished quantity of generated ¹⁴CO₂. Although autologous normal plasma significantly increased all facets of normal lymphocyte glycolysis, autologous leukemic plasma failed to stimulate leukemic lymphocytes in a similar manner. In certain instances, this plasma further depressed neoplastic lymphocyte glucose utilization. These observations are consistent with the hypothesis that leukemic lymphocyte glycogenosis may be a consequence of an augmented pool of one or several glycolytic intermediates ultimately available for glycogen synthesis, and with the idea that leukemic plasma restricts in vivo glucose utilization leading to clinically detected abnormal carbohydrate metabolism in many patients with CLL.