Alteration of Methotrexate by leukemic cells: loss of affinity for an anion exchange resin.

Methotrexate accumulated in the leukemic cells of two of four patients in excess of the concentration expected from the level of inactivated folate reducÃ-aseand could not be removed from the cell lysates by the aniÃ3nexchange resin Dowex 2-X8. In one of these two patients, free folate reducÃ-asewas 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 Ihe leukemic cells of Ine oÃ-her two patients had Methotrexate-bound enzyme, they contained no free folate reducÃ-ase, and the drug could be removed from ihe cell lysaies by similar treaÃ-menÃwith the aniÃ3n exchange resin. In addition, ihese leukemic cells appeared lo be more sensilive io Methotrexate than ihe cells from which the drug could not be removed by the exchange resin. Since free Methotrexate-3 H and most of the enzyme-