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- ItemSomente MetadadadosDeterminação do perfil lipídico metabolômico plasmático, por espectrometria de massas, de pacientes com neoplasias mieloproliferativas crônicas, síndromes mielodisplásicas e leucemia mieloide aguda(Universidade Federal de São Paulo (UNIFESP), 2015-03-25) Oliveira, Adriana Ramos de [UNIFESP]; Chauffaille, Maria de Lourdes Lopes Ferrari Chauffaille [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: There are thousands of individual lipid species in the cells interacting in different compartments in the cell membrane. The functional consequences of this diversity are not yet fully understood and new technological tools are being developed with the aim of a more comprehensive investigation. Over the past two decades, mass spectrometry (MS) has emerged as the main method used in lipidomics analysis, which allows the structural characterization and quantification of complex lipids and their metabolites. Due to the importance of this field we have considered the use of the lipidomic innovative platform to identify differences in the plasma lipid metabolomic profile of hematological patients with Myeloid Neoplasms. Purpose: Determine the lipid metabolomic profile comparative of blood plasma samples from healthy individuals and patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Acute Myeloid Leukemia and evaluate the existence of possible biomarkers. Methods: Untargeted Shotgun MS/MS Analysis was performed from plasma samples from 153 participants were analyzed being, 90 of the Control Group, 43 Myeloproliferative Neoplasms, 11 Myelodysplastic Syndromes and 9 Acute Myeloid Leukemias. Data were acquired using the AB-Sciex Analyst TF, processed using the AB-Sciex LipidView? and the web-based analytical pipeline MetaboAnalyst 2.0. 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 Phosfatidyletanilamines (DMPE), Monometylphosphatidiletanolamines (MMPE), Ceramide-1-phosphate (CerP), Glicerophosphoglycerols (GP), Lysomonomethyl-Phosphatidyl ethanolamines (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 with MDS or AML (Sensitivity= 0.95 (0.824-1); Specificity= 0.8941 (0.847-0953); Positive Likelihood Ratio= 8.972 and Negative Likelihood Ratio =0.05592 and T Test= 7.576E-12). In addition these lipids were also able to differentiate MDS and AML from NMP (Sensitivity= 0.9118 (0.824-1), Specificity= 0.95 (0.85-1); Positive Likelihood Ratio= 18.2 and Negative Likelihood Ratio= 0.05592). Conclusions: The Myeloproliferative Neoplasms from the point of view of global plasma lipidomics are accompanied by several modifications. In particular the Lysomonomethyl-Phosphatidyl ethanolamines seems to play important differentiating roles among them.