Daunorubicin Metabolism in Acute Myelocytic Leukemia

Daunorubicin reductase is a cytoplasmic enzyme that converts daunorubicin to a principal metabolite, daunorubicinol, in the presence of NADPH. This enzyme, found in mammalian tissues and studied in rat tissue preparations and normal human blood components, is also present in human leukemic myeloblasts. The enzymes from both normal and leukemic leukocytes require NADPH for activity, have similar kinetics and substrate saturation characteristics, and have a K_m, of 1.7 x 10^-4M. When daunorubicin reductase levels in leukemic myeloblasts are related to the clinical response to daunorubicin therapy, we find that patients with a high enzyme level respond favorably to daunorubicin therapy with either a complete or partial remission, whereas those patients with a lower enzyme level experience either no response or die during therapy. These observations suggest that the level of daunorubicin reductase in the leukemic myeloblast may be important in determining the susceptibility of that cell to daunorubicin. Moreover, the measurement of daunorubicin reductase level may have prognostic value regarding the clinical response to daunorubicin therapy.