Effect of (dl)-5-Methyltetrahydrofolate on Acute Non-Lymphocytic Leukemia Cells in Primary Culture

Abstract

High doses of (dl)-5-methyltetrahydrofolate (mTHF) cause strong inhibition of growth of leukemic cell lines. We studied the effect of mTHF, at concentrations ranging from 10(-3) M to 10(-4) M, on peripheral leukemic cells obtained from 15 acute non-lymphocytic leukemia (ANLL) patients, by [3H]-thydimidine uptake inhibition. Unlike leukemic cell lines, mTHF exerts a variable effect on ANLL cells in primary culture. While about 33% of cases are strongly inhibited, 55% are only slightly affected, showing a reduction in growth comparable to normal cell populations tested (unstimulated and PHA-stimulated lymphocytes, day 7 and day 14 colony forming units-granulocyte/monocyte (CFU-GM), normal blast colonies). In a minority of cases we observed stimulation of growth. This study reflects the metabolic variability of single-case leukemic cell populations, possibly in relationship to folate transport and accumulation.