Initial Analysis of Lipid Metabolomic Profile Reveals Differential Expression Features in Myeloid Malignancies

Abstract

The purpose of this preliminary study was to determine the comparative lipid profile of blood plasma samples of healthy individuals and patients with Myeloproliferative Neoplasms. Methods: Untargeted Shotgun MS/MS Analysis was performed to evaluate plasma samples from 153 participants, being 90 of the Control Group, 43 Myeloproliferative Neoplasms (MPN), 11 Myelodysplastic Syndromes (MDS) and 9 Acute Myeloid Leukemias (AML). Lipids were extracted from plasma using the Bligh-Dyer protocol. Data were acquired using the AB-Sciex Analyst TF, processed using the AB-Sciex LipidView TM and the web-based analytical pipeline MetaboAnalyst 2.0 ( www.metaboanalyst.ca ). Results: Untargeted analysis identified in negative and positive-modes a total of 658 features at 2 ppm resolution. PCA and PLS-DA analysis revealed clear discrimination among groups, in particular for AML patients. Main lipid groups differentially expressed were: Monoacylglycerols (MAG), Glucosylceramide E (GlcdE), Ethyl Esters (EE), Lysophosphatidic acid (LPA), Sulfoquinovosil diacylglycerols (SQDG), Monoglycerols (MG), Methyl Ethanolamines (ME), Lysophosphatidylcholines (LPC), Dimethyl Phosfatidyletanolamines (DMPE), Monom etylphosphatidiletanolamines (MMPE), Ceramide-1-phosphate (CerP), Glicerophosphoglycerols (GP), Lysomonomethyl-Phosphatidylethanolamines (LMMPE), Phosphatidic Acids (PA), Ergosterols (ERG), Glycerophosphoserine (PS), Diacylglycerols (DAG), Hexocylceramides (HexCer) and Lanosterol (Lan). ROC Curve Analysis revealed Total LMMPE as the strongest discriminating marker between Controls from Patients. In addition, these lipids were also able to differentiate MDS and AML from NPM. Conclusions: The Myeloproliferative Neoplasms from the point of view of global plasma lipidomics are accompanied by several modifications. In particular, the Lysomonomethyl-Phosphatidylethanolamines (LMMPE) seems to play important differentiating roles among them.