Glucose induced-AKT/mTOR activation accelerates glycolysis and promotes cell survival in acute myeloid leukemia

Multiple studies have demonstrated that excessive glucose utilization is a common feature of cancer cells to support malignant phenotype. Acute myeloid leukemia (AML) is recognized as a heterogeneous disorder of hematopoietic stem cells characterized by altered glucose metabolism. However, the role of glucose metabolic dysfunction in AML development remains obscure. In this study, glucose and 2-Deoxy-D-glucose (2-DG) treatment were applied to analyze the relationship between glucose metabolism and cell survival. Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) assays were used to examine the cell viability and apoptosis rate. Glucose consumption and lactate production were measured to assess the glucose metabolism pathway. The results demonstrated that abnormally increased glucose effectively promoted proliferation of leukemic cells and inhibited cell apoptosis, while 2-DG ameliorated leukemic phenotypes. Importantly, glucose exposure induced active glycolysis by increasing glucose consumption and lactate production. Furthermore, the levels of key glycolysis-related genes glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) were upregulated. Mechanistic investigations revealed that AKT/mTOR signaling pathway was activated in glucose condition. In conclusion, our findings indicate that glucose induced-AKT/mTOR activation plays a growth-promoting role in AML, highlighting that inhibition of glycolysis would be a vital adjuvant therapy strategy for AML.

 

Comments：

The study aimed to investigate the role of glucose metabolism in the development of acute myeloid leukemia (AML). The authors used glucose and 2-Deoxy-D-glucose (2-DG) treatments to examine the relationship between glucose metabolism and cell survival. Cell viability, apoptosis rate, glucose consumption, and lactate production were measured, and the levels of key glycolysis-related genes were analyzed. The results showed that abnormally increased glucose effectively promoted leukemic cell proliferation and inhibited cell apoptosis. In contrast, 2-DG ameliorated leukemic phenotypes. Glucose exposure induced active glycolysis, upregulated the levels of glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1), and activated the AKT/mTOR signaling pathway. The findings suggest that glucose-induced AKT/mTOR activation plays a growth-promoting role in AML, and inhibition of glycolysis may be a vital adjuvant therapy strategy for AML. Overall, the study sheds light on the relationship between glucose metabolism and AML development, providing new insights into potential therapeutic targets for this disease.

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