CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism

Frontiers in Cell and Developmental Biology

Sa Guo¹  Lei Chu¹  Gang Yin²  Wen-Li Huang³  Chao Ji⁴  Kai-Wei Liang⁴  Wei-Wei Zheng⁵  Tuersunayi Abudureheman⁵  Neng Zhou⁵  Jing Xia⁵  Rong-Yi Shi⁵  Jian-Min Zhu⁵  Ming-Hao Li⁵  Hang Zhou⁶  Cai-Wen Duan⁶  Kai Qing⁷ 

[1] Department of Gynecology and Obstetrics, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China;Department of Pathology, School of Basic Medical Science, Central South University, Changsha, China;Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China;Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China;Key Laboratory of Pediatric Hematology and Oncology, Shanghai Children’s Medical Center, Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Collaborative Innovation Center for Translational Medicine, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: CDK9 inhibitors;    cell apoptosis;    glycolysis;    c-Myc;    B-cell acute lymphocytic leukemia;   

DOI  :  10.3389/fcell.2021.641271

来源: DOAJ

【 摘 要 】

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL.

【 授权许可】

Unknown