Methotrexate accumulated in the leukemic cells of two of four patients in excess of the concentration expected from the level of inactivated folate reductase and could not be removed from the cell lysates by the anion exchange resin Dowex 2-X8. In one of these two patients, free folate reductase was assayed in the same cell lysates which, when boiled, appeared to contain an excess of a pharmacologically active inhibitor of this enzyme. In contrast, although the leukemic cells of the other two patients had Methotrexate-bound enzyme, they contained no free folate reductase, and the drug could be removed from the cell lysates by similar treatment with the anion exchange resin. In addition, these leukemic cells appeared to be more sensitive to Methotrexate than the cells from which the drug could not be removed by the exchange resin. Since free Methotrexate-3H and most of the enzymebound drug could be removed from solution by the Dowex 2-X8, it is suggested that some change occurs in the drug in some leukemic cells which alters the drug's affinity for both the anion exchange resin and folate reductase.

1

Supported in part by Grant CA 08976 from the National Cancer Institute of the NIH and the Grossberg Leukemia Foundation.

This content is only available via PDF.