Investigation of pathogenesis and therapeutic targets of acute myeloid leukemia based on untargeted plasma metabolomics and network pharmacology approach

Abstract

Acute myeloid leukemia (AML) is a malignant disease originating from bone marrow hematopoietic stem cells, characterized by anemia, hemorrhage, fever, and infection, with low survival rate. However, the pathogenesis of AML is not fully understood at present. In this work, an integrated approach based untargeted metabolomics and network pharmacology was adopted to elucidate the pathogenesis of AML. Metabolic profiling of plasma samples from 14 patients and 16 healthy individuals were performed based on UHPLC-MS platform. As a result, 23 metabolites were identified by using the human metabolite database based on PLS-DA (partial least squares discriminant analysis) and independent sample test. And metabolic pathways related to AML mainly included fatty acid metabolism, amino acid metabolism, energy metabolism and lipid metabolism. Meanwhile, biomarkers-targets-pathways-disease network was constructed, 75 biomarker targets and 122 disease targets were identified. Furthermore, 30 pathways were predicted, some of which were consistent with these in metabolomics. This is the first time that metabolomics and network pharmacology approach have been combined to investigate the pathogenesis and therapeutic targets of AML. ALDH, CYP2E1 and CYP3A4 were potential therapeutic targets for AML, which provide available way to elucidate the pathogenesis and treatment of AML.