Metabolomic Profiling Reveals Distinct Signatures in Primary and Secondary Polycythemia
Abstract
Background/Objectives: The differential diagnosis between primary polycythemia vera (PV) and secondary polycythemia (SP) presents significant clinical challenges owing to substantial phenotypic overlap. This investigation utilized untargeted metabolomic approaches to elucidate disease-specific metabolic perturbations and evaluate the metabolic consequences of cytoreductive therapeutic interventions. Methods: Plasma specimens obtained from PV patients (n = 40) and SP patients (n = 25) underwent comprehensive metabolomic profiling utilizing liquid chromatography–mass spectrometry (LC-MS) platforms. Multivariate statistical analyses, including principal component analysis (PCA), were employed in conjunction with pathway enrichment analyses to characterize disease-associated metabolic dysregulation. Additionally, receiving treatment (tPV) (n = 25) and not receiving treatment (ntPV) (n = 15) PV patients were compared to assess therapeutic metabolic effects. Results: Comprehensive metabolomic analysis identified 67 significantly altered metabolites between PV and SP patients, with 36 upregulated and 31 downregulated in PV. Key upregulated metabolites in PV included thyrotropin-releasing hormone, 3-sulfinoalanine, nicotinic acid adenine dinucleotide, and protoporphyrin IX, while 4-hydroxyretinoic acid and deoxyuridine were notably downregulated. Pathway enrichment analysis revealed disruptions in taurine, glutamate, nicotinate, and cysteine metabolism in PV. ntPV patients exhibited…
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