Post translational modifications of glucose-6-phosphate dehydrogenase in human leukemias

The modifications of the electrofocusing pattern, the immunological reactivity and the kinetic properties of glucose 6 phosphate dehydrogenase have been studied in malignant blood cells of various leukemias and myeloproliferative disorders. 1. Granulocytic G-6PD forms with decreased isoelectric points have been found in all the acute myeloid leukemias and erythroleukemias, and in most of the chronic granulocytic leukemias and myelofibrosis. In contrast, granulocytic G-6PD from patients with polycythemia vera always was normal. On the same way leukemic lymphocyte or lymphoblast G-6PD was identical to that from normal lymphocytes. 2. The ratio of enzymatic activity to immunological reactivity (=molecular specific activity) was markedly decreased in the myeloblasts of two patients with acute myeloid leukemia, and in the erythroblast-rich cellular fraction of a patient with erythroleukemia. In these cells the decrease of molecular specific activity was parallel to the alteration of the electrofocusing pattern of G-6PD. 3. The enzymatic forms with decreased isoelectric point also exhibited an altered affinity for glucose 6 phosphate. These modifications are post translational alterations of the neosynthesized G-6PD, since this enzyme is a single molecule, coded by the same gene in all tissues; they seem to correspond to an accelerated molecular aging due to an increased concentration of "G-6PD modifying factors". The significance of such an increased concentration of these G-6PD modifying factors in malignant cells is discussed.