Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Fatty acid composition of lymphocyte membrane phospholipids in children with acute leukemia. 1159 88

This study compared the cellular uptake of pure conjugated linoleic acid isomers (CLA(9c,11t) and CLA(9c,11c)) to linoleic acid (LA) and their effects on polyunsaturated fatty acid (PUFA) synthesis, its metabolism into conjugated long chain fatty acids (FAs) by desaturation and chain-elongation as well as cell proliferation and the associated anticarcinogenic effects on various human leukemia cell lines (K562, REH, CCRF-CEM and U937 cells). Furthermore, selective effects of this individual isomers of CLA on desaturation steps involved in the biosynthesis of PUFAs associated with cell growth were investigated. CLA isomers supplemented in the culture medium was readily incorporated and esterified into phospholipids (PLs) in the four cell lines in a concentration- and time-dependent manner. The incorporation of the specific CLA isomers in PLs was similar to LA. All four incubating leukemia cells (40 microM CLA for 48 h) showed very high cellular CLA content in PLs (range: 32-63 g FA/100 g total phospholipid fatty acid) affected by the nature of CLA and the cell type. Supplementation with CLA or LA altered also cell membrane composition by n-6 PUFA synthesis. Accordingly, CLA metabolism interferes with LA metabolism. We were able to show that CLA isomers are converted by the leukemia cells of the same metabolic pathway into conjugated diene fatty acids (CDFAs) as LA into non-conjugated PUFAs. In this view, the gas chromatography-flame ionization detector detection of major CDFAs (CD-18:3, CD-20:2 and CD-20:3) in cell membrane of CLA-treated cultures resulted from successive Delta6-desaturation, elongation and Delta5-desaturation of CLA isomers. However, in comparison to LA, relatively lower amounts of elongation and/or desaturation metabolites were detected for CLA(9c,11t), and only minor amounts or trace CDFAs were observed for CLA(9c,11c). Furthermore, CLA(9c,11t) revealed only very low levels of CD-20:4 FA and no CLA(9c,11c)-conversion could be detected. The metabolization of CLA indicated that CLA(9c,11c)<CLA(9c,11t) were a poorer substrates in compared to LA for the Delta5,6-desaturation/elongation in REH, CCRF-CEM and U937 cells or for the Delta5-desaturation/elongation in the K562 cells. CLA(9c,11t) suppresses Delta6-desaturation in CCRF-CEM, REH, and U937 cells (43.5, 54.6 and 58.8% Delta6-inhibition, respectively) and as well Delta9-desaturation in all four cell lines (Delta9-inhibition; 47.1, 33.9, 29.8 and 25.9% for CCRF-CEM, REH, K562 and U937 cells, respectively). However, CLA(9c,11c) does not inhibit or only slightly affected these desaturations. CLA(9c,11t) isomer was found as an Delta6-desaturase inhibitor with a dose-dependent relationship between inhibition of Delta6-desaturase activity and decreases in cell growth. The growth inhibitory effects of CLA (with 30-120 microM) on leukemia cells were dependent upon the type and concentration of CLA isomers present. CLA-supplemented cells with low concentrations (<60 microM) were not sufficient to impair cell proliferation. Nevertheless, higher amounts of CLAs (>60 microM) had the CLA type dependent antiproliferative effects. Thus, the 9cis,11trans- and the 9cis,11cis-CLA isomers regulate cell growth and survival in different leukemia cell types through their existence alone and/or by their inhibitory effects of desaturase activity.
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PMID:Conjugated linoleic acid modulation of cell membrane in leukemia cells. 1514 24