Dysregulated Bioactive Lipid Profiles Characterize Inflammation in Philadelphia-Negative Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are clonal hematological disorders defined by myeloproliferation driven by genetic mutations. Beyond these genetic changes, inflammation is a key contributor to the MPNs pathophysiology and influencing clinical outcomes. Among the mediators of inflammation, bioactive lipids (BL) are critical due to their involvement in all stages of inflammation process, from initiation to resolution. BL constitute a major component of cell membranes, act as efficient energy sources, and regulate numerous inter- and intracellular processes. Thus, this study investigated lipid metabolism alterations in MPNs using liquid chromatography, mass spectrometry, and bioinformatics. The 5-HETE and 15-HETE were elevated in ET and PV, respectively, and PV exhibited the most diverse eicosanoid profile among MPN categories. The results revealed distinct MPN metabolomic signatures, with pathways such as bile acid biosynthesis and fatty acid oxidation enriched in ET and PMF, and pathways like sphingolipid metabolism and vitamin E metabolism altered in PV. Integrative molecular networks indicated the cytokine, eicosanoid, and metabolite associations for each MPN subtype. Taken together, the findings underscore the potential of lipidomic and metabolomic profiling to uncover disease-specific mechanisms, identify novel biomarkers, and metabolic targets for therapeutic intervention in MPN.