Enzyme Activities and Deoxynucleoside Utilization of Leukemic Leukocytes in Relation to Drug Therapy and Resistance¹

The activity of dihydrofolate reductase, thymidylate synthetase, thymidine kinase, and uridine kinase has been examined in leukocytes from untreated patients with acute or chronic leukemia. Based on the correlations between percent of blast cells, leukocyte count, level of enzyme activity, and the activity of deoxyuridine and thymidine incorporation into DNA, blast cells from patients with acute lymphocytic leukemia appear to be more homogeneous than blast cells from patients with acute granulocytic leukemia or immature cell types of chronic granulocytic leukemia. With the exception of changes in dihydrofolate reductase activity following Methotrexate, the changes in enzyme activity with drug therapy were probably the result of shifts in the percentage of blast cells in the leukocyte population. Normal, or near normal, levels of enzyme activity were observed in leukocytes from patients with acute leukemia in remission. Resistance to Methotrexate, mercaptopurine, and cyclophosphamide was associated with pretreatment ranges of enzymatic activity. No significant difference was observed in dihydrofolate reductase activity of leukocytes from untreated patients with acute leukemia or from patients in remission, relapse, or resistance to Methotrexate. Leukocytes from patients with acute leukemia or chronic granulocytic leukemia incorporated deoxyuridine and thymidine into DNA as effectively as specimens of normal marrow or marrow from patients with acute granulocytic leukemia.