Document Type

Article

Publication Title

Acta Pharmaceutica Sinica B

Abstract

Acute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics. This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle, coupled with an upregulation of the creatine metabolism. The upregulation of creatine synthetases Gatm and Gamt, as well as the creatine transporter Slc6a8, resulted in a marked accumulation of creatine within tumor foci. This process further enhances oxidative phosphorylation and glycolysis of leukemia cells, thereby boosting ATP production to foster proliferation and infiltration. Importantly, we discovered that inhibiting Slc6a8 can counter these detrimental effects, offering a new strategy for treating AML by targeting metabolic pathways.

DOI

10.1016/j.apsb.2024.07.004

Publication Date

7-6-2024

Keywords

Spatial metabolomics, Acute myeloid leukemia, Metabolic reprogramming, Creatine, Slc6a8, Oxidative phosphorylation, Glycolysis, Metastasis

ISSN

2211-3843

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