Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients.

Abstract

Dihydrofolate reductase activity was found to be highly heterogeneous in terms of its specific activity and methotrexate sensitivity in the blast cells of patients with acute myelogenous leukemia. None of the patients had previously been treated with methotrexate (MTX). The blast cells of four of 12 patients studied contained methotrexate-insensitive forms of dihydrofolate reductase, and the blast cells of three (distinct from the four mentioned previously) of the 12 had significantly higher dihydrofolate reductase activities than the rest. The presence of MTX-insensitive dihydrofolate reductases and high levels of enzyme activity represent intrinsic mechanisms of resistance and may explain the apparent clinical resistance of acute myelogenous leukemia to methotrexate.