A Macromolecular Factor in Some Leukemic Cells Which Binds Folic Acid 1

Abstract

Summary

The reduction of 0.57 μμmoles of ³H-folic acid to tetrahydrofolic acid by folate reductase in the cell lysates from two patients with chronic myelogenous leukemia was not apparent until the total substrate concentration of the reaction mixture was raised by the addition of stable folic acid. In addition, these leukemic cell lysates inhibited the reduction of tracer ³H-folic acid by a leukemic cell lysate containing “normal” folate reductase activity. Gel-filtration experiments demonstrated that this phenomenon was due to binding of the tracer folate to a large molecule because ³H-folic acid preincu-bated with these peculiar leukemic cell lysates and filtered through Sephadex G-75 appeared in the early or excluded volume indicating that the substrate was bound to a factor with a molecular weight of at least 50,000. This binding of ³H-folic acid could be competitively inhibited by stable folate.

I thank Carol Schreiber for her technical assistance for part of these studies, and Drs. Robert Goldstein and Solomon Berson for their helpful criticism in the preparation of this manuscript.