gamma-linolenic-acid and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

The composition of phospholipid fatty acids (PLFA) of separated mononuclear blood cells (MNC) from patients with leukemia was established by high-resolution gas chromatography. Abnormal fatty acid concentrations are detected in the MNC membrane phospholipids in patients with acute lymphoblastic leukemia (ALL) without a deficiency of essential fatty acids (EFA). Significantly reduced relative levels of linoleic acid (4.35 vs. 7.82%; P<0.001) are found in the MNC-PL in patients with ALL as compared to a healthy control group. Moreover, the Delta6-desaturated fatty acids are increased: gamma-linoleic acid (3.56 vs. 0.17%; P<0.001), arachidonic acid (21.82 vs. 16.27%; P<0.05), docosatetraenoic acid (3.52 vs. 1.56%; P<0.001), docosapentaenoic acid (0.34 vs. 0.04%; P<0.001), octadecatetraenoic acid (0.53 vs. 0.23%; P<0.05), eicosatetraenoic acid (1.83 vs. 0.08%; P<0.001) and docosahexaenoic acid (2.77 vs. 1.54%; P<0.001). A increased Delta(6)-desaturase activity is postulated as the cause for the increased level of desaturate products or the increased Delta6-activity index (Ratio of gamma-linoleic acid+dihomogamma-linolenic acid to linoleic acid) (1.21 vs. 0.27; P<0.001). The Delta6-enzyme activities measured using linoleic acid and alpha-linoleic acid as substrate underscore these findings (Delta6(n-6); 2.49 vs. 0.65 and Delta6(n-3); 2.75 vs. 1.12 nmol x h(-1)/10(8) MNC). In contrast, patients with acute myeloid leukemia (AML) do not show any significant differences in the lymphocyte membrane PLFA and no Delta6-desaturase abnormalities.

Topics: Adolescent; alpha-Linolenic Acid; Arachidonic Acid; Cell Membrane; Child; Child, Preschool; Chromatography, Gas; Erucic Acids; Fatty Acids; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Humans; Leukemia, Myeloid, Acute; Lymphocytes; Male; Phospholipids; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The polyunsaturated fatty acids (PUFAs), linoleic acid (LA), alpha linolenic acid (ALA), gamma linolenic acid (GLA), arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), showed inhibition of growth of both normal and abnormal (Molt-4) human lymphocytes, and inhibition was concentration-dependent. Interestingly, the production of the lymphokine Interleukin-2 (IL-2) was elevated in Molt-4 cells, but it was reduced in the normal human lymphocytes. Addition of GLA or IL-2 or a combination of both showed enhancement of SO2.- and of lipid peroxidation levels, which were significantly higher in Molt-4 cells than in the normal lymphocytes. Reduction of protein concentration was also observed in both types of cells during this treatment. The data showed that the antiproliferative effects of GLA and IL-2 may partly be exerted through the elevated production of superoxide free radicals and peroxidation products. This is a novel finding and therefore, further exploitation of combinations of PUFAs and IL-2 may be a possible way of combating cancer cell growth.

Topics: Cell Line; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Humans; Interleukin-2; Lipid Peroxidation; Lymphocyte Activation; Lymphocytes; Malondialdehyde; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Structure-Activity Relationship; Tumor Cells, Cultured