Clinico-Metabolic Profiling Unraveled Key Metabolic Alterations Underlying the Pathophysiology of Chronic Myeloid Leukemia

H nuclear magnetic resonance (NMR) spectroscopy, followed by multivariate and univariate statistical approaches. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Thirty-eight metabolites were identified, and multivariate analysis revealed significant metabolic disparity between CML and control subjects with substantial alterations in amino acid and energy metabolism. Key eight metabolites, including histidine, alanine, valine, glutamine, tyrosine, serine, glucose, and isoleucine, demonstrated consistent downregulation in CML, reflecting enhanced cellular uptake and metabolic rewiring characteristic of leukemic proliferation. Depletion of branched-chain amino acids and increased reliance on glutamine and glycolytic intermediates highlight vulnerabilities that may be exploited for therapeutic intervention. ROC analysis demonstrated promising discriminatory ability of these metabolites in this cohort, with several achieving an area under the ROC curve (AUROC) > 0.90, suggesting their potential as biomarkers in this cohort their utility . Serum metabolomics reveals a distinct CML signature marked by enhanced bioenergetic and biosynthetic demands, immune evasion, and drug resistance mechanisms. These findings underscore the potential of serum metabolic profiles as noninvasive biomarkers at the exploratory discovery stage, while also providing preliminary pathophysiological insights that may guide future studies on metabolism-targeted therapeutic strategies.