Caracterização metabolômica global em plasma de pacientes com leucemia linfoblástica aguda e leucemia mieloide aguda.

Abstract

Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are hematologic neoplasms that result in quantitative and qualitative alterations of blood cells. Both hematologic neoplasms have genetic limitations to staging systems, favoring the search for clinical and biological markers that can improve the evolutionary prediction of these diseases. Thus, the general objective of this study was to identify differentiating metabolites present in the plasma of patients with acute leukemias in relation to the control group through the global metabolic approach, using the liquid chromatography coupled to mass spectrometry (LC-MS) technique. Plasma samples from 27 patients with ALL and 26 patients with AML, at different collection times, from the Hospital das Clínicas of the Federal University of Minas Gerais and from 32 healthy individuals who constituted the control group were analyzed in the study. The assay generated 4.241 and 6.688 molecular characteristics respectively in the negative and positive acquisition modes. The data were analyzed by multivariate and univariate statistical methods to create the ranking of discriminating characteristics between the studied groups. For the ALL (T0) vs. CTRL group, 30 metabolites were selected with the following class distribution: 50% lipids that fall into four categories (acyl lipid, sphingolipid, glycerophospholipid and glycosphingolipid); 13% bile acids; 10% drugs, 3% nucleosides and 24% still ‘unknown’, all with increased intensity in ALL patients. In the analysis of the temporal collections of the ALL group, when compared with the control group, the metabolites identified with decreased intensity are from the class of dicarboxylic acids and leukotrienes B4/B5, and the main ones with increased intensity were taurocholic acid, sphingosine, phosphatidic acid, LPE O (20:4), LysoPE (14:1), CDP-DG and ganglioside GA1/GB4, it seems that no considerable differences were observed in these metabolites at the different collection times. In the evaluation of the AML group (T0) vs. CTRL, the 30 main differentiating metabolites with increased intensity in AML were chosen, belonging to the class of lipids (sphingolipids; glycerophospholipids), bile acids, amino acids, nucleosides, drugs and some still unknown. To investigate the temporal collections of the AML group from the heatmap, 25 main metabolites presented decreased intensity in patients with AML, related to the class of dicarboxylic acids and leukotrienes and with increased intensity of taurocholic acid; sphingosine C17; vitamin D derivative and phosphoric acid when compared to the control group. The metabolic phenotype profile does not appear to have major variations in intensity over the three weeks analyzed. When comparing the two groups ALL and AML from the set of 30 metabolites of each group, it was identified that there are 8 metabolites exclusive to the ALL group (T0), 12 metabolites exclusive to the AML group (T0) and 16 metabolites in common between the two leukemias. The metabolites revealed in this study appear to be indicated in important biological pathways related to immune regulation processes such as inflammation, acting on the RAF/MEK/ERK, PI3K/AKT (mTOR) signaling cascades, angiogenesis, cell signaling processes, cellular energy metabolism and intestinal microbiota.