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

• Published in: Leukemia research 2023-05, Vol.128, p.107059-107059, Article 107059
• Main Authors: Chen, Shana, Tao, Yonghong, Wang, Qian, Ren, Jun, Jing, Yipei, Huang, Junpeng, Zhang, Ling, Li, Rufei
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; AKT/mTOR signaling pathway; Cell Line, Tumor; Cell Proliferation; Cell Survival; Glucose; Glucose - metabolism; Glucose - pharmacology; Glycolysis; Humans; Lactates - pharmacology; Leukemia, Myeloid, Acute - genetics; Proto-Oncogene Proteins c-akt - metabolism; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2023.107059

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. [Display omitted] •Glucose treatment promotes leukemic cell growth and inhibits cell apoptosis.•Glucose treatment induces glycolysis in leukemic cells.•AKT/mTOR signaling pathway is involved in glycolysis and leukemic cell survival.