1. Academic Validation
  2. Glucose induced-AKT/mTOR activation accelerates glycolysis and promotes cell survival in acute myeloid leukemia

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

  • Leuk Res. 2023 Mar 22;128:107059. doi: 10.1016/j.leukres.2023.107059.
Shana Chen 1 Yonghong Tao 2 Qian Wang 1 Jun Ren 2 Yipei Jing 2 Junpeng Huang 2 Ling Zhang 2 Rufei Li 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Chonggang General Hospital, Chongqing 400080, China.
  • 2 Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing 400016, China.
  • 3 Department of Laboratory Medicine, Chonggang General Hospital, Chongqing 400080, China. Electronic address: RufeiLi258369@126.com.
Abstract

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.

Keywords

AKT/mTOR signaling pathway; Acute myeloid leukemia; Cell survival; Glucose; Glycolysis.

Figures
Products