Identification of glucuronic acid as a biomarker of poor prognosis in acute myeloid leukemia based on plasma metabolomics.

Metabolic abnormalities have been identified in various solid tumors and hematologic diseases, with reprogramming of central carbon metabolism occurring to promote disease progression. However, the metabolic profile of central carbon in acute myeloid leukemia (AML) remains unknown. We employed targeted metabolomics to analyze the alterations in central carbon metabolites present in the blood of acute myeloid leukemia (AML) patients. Models constructed using orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to evaluate intergroup differences in metabolite levels. Furthermore, a public database facilitated the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Additionally, metabolites exhibiting significant differences were selected, and their effects on the proliferation and drug resistance of human myeloid leukemia cell lines were validated in vitro using CCK-8 analysis, MTT assays, and flow cytometry. Our results indicated that 27 targeted metabolites were up-regulated and eight targeted metabolites were down-regulated in the AML group. These metabolites were primarily enriched in pathways related to the biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, glucagon signaling, 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, the citrate cycle (TCA cycle), and central carbon metabolism in cancer. Notably, significant changes were observed in malic acid, alpha-ketoisovaleric acid, and glucuronic acid. In vitro experiments demonstrated that exogenous glucuronic acid can promote the growth and drug resistance of human AML cells. In conclusion, this study reveals alterations in central carbon metabolites in the blood of AML patients and identifies metabolites that may play a role in AML development and drug resistance.