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), Monometylphosphatidiletanolamines (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.

Pisum sativum Defensin 1 Eradicates Mouse Metastatic Lung Nodules from B16F10 Melanoma Cells

“…Some lipids and their metabolites are also involved in apoptosis, inflammation, angiogenesis, and cell proliferation signaling [63]. It is known that several cancer cell types suffer lipid metabolism reprogramming when compared to non-cancerous cells [27,36,64]. As an example, phosphatidylserine (PS), before being present in the membrane inner leaflet, is externalized [65], and cholesterol synthesis increases [27,66,67].…”

“…It is found in most fungi, except in Saccharomyces cerevisiae and Candida glabrata [33] and is conserved in higher eukaryotes, such as plants and mammals. They are essential for cellular structural integrity and regulating the fluidity of the lipid bilayer and are involved in cell proliferation [34,35], differentiation [27,36], and oncogenic transformation [37,38].…”

Integrative metabolic profile of myelodysplastic syndrome based on UHPLC–MS

“…Saurina and Sentellas (2017) applied the LC–quadrupole time‐of‐flight–MS platform to monitor the levels of prostaglandins in the bone marrow mesenchymal stromal cells. Lysomonomethyl–phosphatidylethanolamines and other lipid metabolites have been identified as potential biomarkers of myeloid malignancies (de Oliveira et al, 2015). In patients with MDS, the level of 2‐hydroxyglutarate in myeloid lineage cells is increased.…”