The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features.

Pabst, Thomas; Kortz, Linda; Fiedler, Georg Martin; Ceglarek, Uta; Idle, Jeffrey; Beyoglu, Diren (2017). The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features. BBA clinical, 7, pp. 105-114. Elsevier 10.1016/j.bbacli.2017.03.002

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BACKGROUND 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Pabst, Thomas; Fiedler, Georg Martin; Idle, Jeffrey and Beyoglu, Diren

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2214-6474

Publisher:

Elsevier

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

07 Feb 2018 17:16

Last Modified:

14 Mar 2018 12:41

Publisher DOI:

10.1016/j.bbacli.2017.03.002

PubMed ID:

28331812

Uncontrolled Keywords:

12-HEPE, 12-hydroxy-5Z,8Z,10E,14Z,17Z-eicosapentaenoic acid 12-LOX, 12-lipoxygenase 2HG, (R)-2-hydroxyglutarate 2OG, 2-oxoglutarate 8,9-DHET, 8,9-dihydroxy-5Z,11Z,14Z-eicosatrienoic acid AA, arachidonic acid ALL, acute lymphoblastic leukemia AML, acute myeloid leukemia Acute myeloid leukemia Blast cell number CE, cholesterol ester CML, chronic myelogenous leukemia CPT1a, carnitine palmitate transferase 1a Cer, ceramide CoQ10, coenzyme Q10 DG, diacylglycerol DGLA, dihomo-γ-linoleic acid DIC, disseminated intravascular coagulation EPA, eicosapentaenoic acid (20:5;5Z,8Z,11Z,14Z,17Z) ESI-, electrospray ionization negative mode ESI +,  electrospray ionization positive mode Eicosanoids FAA, fatty acid amide FAB, French-American-British classification FAME, fatty acid methyl ester FAO, fatty acid oxidation FLC-QqLIT-MS, fast liquid chromatography-quadrupole linear ion-trap mass spectrometry Fatty acids GCMS, gas chromatography–mass spectrometry LPC, lysophosphatidylcholine LPE, lysophosphatidylethanolamine Lipidomics MG, monoacylglycerol MRM, multiple reactions monitoring MUFA, monounsaturated fatty acid OPLS-DA, orthogonal PLS-DA PC, phosphatidylcholine PCA, principal components analysis PE, phosphatidylethanolamine PGE2, prostaglandin E2 PGF1α, prostaglandin 1α PGF2α, prostaglandin F2α PGH2, prostaglandin H2 PLS-DA, projection to latent structures-discriminant analysis POEA, palmitoleoyl ethanolamide PUFA, polyunsaturated fatty acid Prognostic risk SCD1, stearoyl CoA desaturase 1 SM, sphingomyelin TG, triacylglycerol (triglyceride) TxA2, thromboxane A2 TxB2, thromboxane B2 UPLC-ESI-QTOFMS, ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry mPGES-1, microsomal prostaglandin E synthase-1

BORIS DOI:

10.7892/boris.109269

URI:

https://boris.unibe.ch/id/eprint/109269

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