Pabst, Thomas NiklausThomas NiklausPabstKortz, LindaLindaKortzFiedler, Georg MartinGeorg MartinFiedlerCeglarek, UtaUtaCeglarekIdle, JeffreyJeffreyIdleBeyoglu, DirenDirenBeyoglu2024-10-252024-10-252017-06https://boris-portal.unibe.ch/handle/20.500.12422/157060BACKGROUND Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors. METHODS Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors. Data were collected on total cholesterol and fatty acids, fatty acid amides, glycerolipids, phospholipids, sphingolipids, cholesterol esters, coenzyme Q10 and eicosanoids. RESULTS We observed a depletion of plasma total fatty acids and cholesterol, but an increase in certain free fatty acids with the observed decline in sphingolipids, phosphocholines, triglycerides and cholesterol esters probably driven by enhanced fatty acid oxidation in AML cells. Arachidonic acid and precursors were elevated in AML, particularly in patients with high bone marrow (BM) or peripheral blasts and unfavorable prognostic risk. PGF2α was also elevated, in patients with low BM or peripheral blasts and with a favorable prognostic risk. A broad panoply of lipid classes is altered in AML plasma, pointing to disturbances of several lipid metabolic interconversions, in particular in relation to blast cell counts and prognostic risk. CONCLUSIONS These data indicate potential roles played by lipids in AML heterogeneity and disease outcome. GENERAL SIGNIFICANCE Enhanced catabolism of several lipid classes increases prognostic risk while plasma PGF2α may be a marker for reduced prognostic risk in AML.en12-HEPE12-hydroxy-5Z8Z10E14Z17Z-eicosapentaenoic acid 12-LOX12-lipoxygenase 2HG(R)-2-hydroxyglutarate 2OG2-oxoglutarate 89-DHET89-dihydroxy-5Z11Z14Z-eicosatrienoic acid AAarachidonic acid ALLacute lymphoblastic leukemia AMLacute myeloid leukemia Acute myeloid leukemia Blast cell number CEcholesterol ester CMLchronic myelogenous leukemia CPT1acarnitine palmitate transferase 1a Cerceramide CoQ10coenzyme Q10 DGdiacylglycerol DGLAdihomo-γ-linoleic acid DICdisseminated intravascular coagulation EPAeicosapentaenoic acid (20:5;5Z8Z11Z14Z17Z) ESI-electrospray ionization negative mode ESI + electrospray ionization positive mode Eicosanoids FAAfatty acid amide FABFrench-American-British classification FAMEfatty acid methyl ester FAOfatty acid oxidation FLC-QqLIT-MSfast liquid chromatography-quadrupole linear ion-trap mass spectrometry Fatty acids GCMSgas chromatography–mass spectrometry LPClysophosphatidylcholine LPElysophosphatidylethanolamine Lipidomics MGmonoacylglycerol MRMmultiple reactions monitoring MUFAmonounsaturated fatty acid OPLS-DAorthogonal PLS-DA PCphosphatidylcholine PCAprincipal components analysis PEphosphatidylethanolamine PGE2prostaglandin E2 PGF1αprostaglandin 1α PGF2αprostaglandin F2α PGH2prostaglandin H2 PLS-DAprojection to latent structures-discriminant analysis POEApalmitoleoyl ethanolamide PUFApolyunsaturated fatty acid Prognostic risk SCD1stearoyl CoA desaturase 1 SMsphingomyelin TGtriacylglycerol (triglyceride) TxA2thromboxane A2 TxB2thromboxane B2 UPLC-ESI-QTOFMSultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry mPGES-1microsomal prostaglandin E synthase-1600 - Technology::610 - Medicine & healtharticle10.7892/boris.1092692833181210.1016/j.bbacli.2017.03.002