Fatty acids and the inhibition of mitogen-induced lymphocyte transformation by leukemic serum.

The effects of sera from 23 patients with acute lymphocytic leukemia on mitogen-induced transformation of normal human lymphocytes were examined. All sera (100%) at diagnosis and 70% of those obtained during the induction of remission demonstrated inhibition of mitogen-induced lymphocyte transformation as evidenced by decreased uptake of [3H]thymidine. The inhibition could not be overcome by an increase in the mitogen concentration. Eighteen sera demonstrating a mean inhibition of 44.2% had elevated levels of free fatty acids (FFA) compared with five sera showing no inhibition (p value = 0.001). Inhibition, within the range produced by leukemic sera, could be achieved by the purified methyl esters of linoleic and linolenic acid in this system. Flow cytometric analysis of mitogen-induced cycling of normal human lymphocytes suggested that deoxyribonucleic acid (DNA) replication was inhibited by leukemic sera containing elevated levels of FFA after the G1 phase of cell cycling. Similar inhibition could be achieved by the methyl ester of linolenic acid in this system. Gas chromatographic analysis revealed that sera demonstrating inhibition contained linolenic (C18:3) acid (p value = 0.015), and the majority showed one or more of the following: 1) a concentration of oleic (C18:1) acid greater than 2 standard deviations (SD) above the mean of the control leukemic sera (i.e., those not demonstrating inhibition); 2) an arachidonic (C20:4) to C18:1 ratio that is reduced to greater than 2 SD below the mean of the control group; or 3) the presence of an unexpected fatty acid fraction. The data raise the question of an influence of FFA and, specifically, an interplay of unsaturated fatty acids on immune function during the natural history of acute lymphocytic leukemia.