Abstract
Abstract
[Abstract] Objective
: Metabolic reprogramming may contribute to leukemic cell survival and treatment response in acute lymphoblastic leukemia (ALL). This study aimed to characterize dynamic metabolic remodeling during induction chemotherapy and evaluate its association with early treatment response.
Methods
: Sixteen children with newly diagnosed ALL were enrolled. Paired serum samples were collected before and at the end of induction chemotherapy and analyzed using untargeted liquid chromatography–mass spectrometry-based metabolomics. Differential metabolites were identified using multivariate and univariate analyses, followed by pathway enrichment analysis. Changes in selected metabolites were correlated with hematological recovery velocities and minimal residual disease (MRD) status on days 15 and 33.
Results
: Induction chemotherapy induced pronounced metabolic remodeling, with lipid-related metabolites showing the most prominent alterations. Differential metabolites were mainly enriched in phospholipid-, glycerophospholipid-, ether lipid-, and sphingolipid-related pathways. Six representative lipid metabolites, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LysoPC), and sphingomyelin (SM) species, were further analyzed. Spearman analysis showed that several metabolite changes were moderately associated with hematological recovery. The change in PC(16:0/18:1) was negatively correlated with platelet recovery velocity (r = − 0.671) and positively correlated with day-33 MRD status (r = 0.575). PC(P-16:0/18:1) was negatively correlated with day-33 MRD status (r = − 0.547). Changes in PE(18:0/18:2) were negatively correlated with WBC and neutrophil recovery velocities (r = − 0.590 and − 0.574, respectively).
Conclusions
: Induction chemotherapy is associated with substantial lipid metabolic remodeling in children with ALL. Dynamic alterations in specific lipid metabolites are associated with hematological recovery and MRD status, providing preliminary evidence for further investigation of lipid metabolism in early treatment response and MRD persistence.