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.