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DNA synthesis in chronic myelogenous leukemia cells: comparison of results in cells containing folate binding factor to replicating cells without binder.

Some chronic myelogenous leukemia (CML) cells contain a factor with binding determinants for folic acid (PGA), dihydrofolic acid (FH2) and methotrexate (MTX). To determine whether this factor may have some effect on DNA synthesis and the pharmacologic activity of the folate antagonists, the effect of deoxyuridine (dU), PGA, FH2, and MTX, on the incorporation of 3H-dU and 3H-thymidine (3H-TdR) into DNA was compared in short-term cultures of CML cells containing a high and low concentration of binder and in bone marrow cells with no binder. The following observations were made in CML cells with high binder: greater inhibition of 3H-dU incorporation into DNA by 102 pmoles of stable dU; lesser or no stimulation of 3H-dU incorporation into DNA by FH2 and PGA; inhibition rather than stimulation of 3H-TdR incorporation into DNA by FH2, PGA, and MTX; and reversal of these effects when this CML patient was given oral PGA and unsaturated binder concentration in the cells decreased. These findings suggest that the presence of a high concentration of unsaturated folate binder in replicating cells can affect the capacity for de novo DNA synthesis, probably by binding FH2. In addition, because of binding determinants for MTX, the pharmacolgic activity of this drug can also be altered.