METABOLIC PROFILE OF BONE MARROW PLASMA IN MYELOPROLIFERATIVE NEOPLASMS

Abstract

Bioactive lipids have been related to several biological functions such as immune system regulation, angiogenesis, cell survival, and proliferation. They are categorized into eight families: fatty acyls (fatty acids and eicosanoids), glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, polyketides, and saccharolipids. The deregulation of bioactive lipids secretion and production has been shown to contribute to cancer pathogenesis. To quantify eicosanoids levels in bone marrow plasma from myeloproliferative neoplasms patients and healthy subjects. Nine polycythemia vera (PV), 8 primary myelofibrosis (PMF) and 8 essential thrombocythemia (ET) patients at diagnosis and 8 healthy subjects (CT) were investigated. CT group was composed by 4 males and 4 females with a median age of 43 years (y). The PV group was composed by 5 males and 4 females, median age of 61 y; ET group was composed of 1 male and 7 females, median age of 58, and, PMF group was composed by 3 female and 5 males, median age of 68 y. Bone marrow plasma samples were analyzed by high performance liquid chromatography followed by mass spectroscopy. The metabolomics analyzes were performed by using the mass spectral data acquired with negative electrospray ionization and the full scan of the mass/charge ratio (m/z) from 100 to 1500. The results showed that 7346 bioactive lipids compounds were detected in bone marrow plasma from patients and controls. Among all the analyzed compounds we found that 129 of them overlap between all comparisons, as 241 are specific to PMF, 873 to PV and 374 to ET. The predictive analysis of activity of metabolic pathways showed that for PMF and ET, the main deregulated metabolic pathways are bile acid biosynthesis and fatty acid oxidation, while for in PV the deregulated pathways are: arginine and proline metabolism, biopterin metabolism, glutamate metabolism, Glycosphingolipid biosynthesis, Glyoxylate and Dicarboxylate Metabolism, Pyruvate Metabolism, Phytanic acid peroxisomal oxidation, Sphingolipid metabolism, Vitamin E metabolism, Polyunsaturated fatty acid biosynthesis and Xenobiotics metabolism. These data suggest that the bone marrow microenvironment from MPN patients is deregulated, culminating in the deregulation of bioactive lipids and several metabolic pathways. Each disease category presents a metabolic signature, which could be used as biomarker for diagnosis and prognosis and therapeutic target. CAPES, CNPq and FAPESP (2018-01756-5; 2018/18714-7). Metabolomic analysis; Polycythemia vera; Essential thrombocythemia; Primary myelofibrosis.