期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.641271
关键词
CDK9 inhibitors; cell apoptosis; glycolysis; c-Myc; B-cell acute lymphocytic leukemia
资金
- National Key RAMP
- D Program of China, Stem Cell and Translation Research [2016YFA0102000, 2019YFA0111100]
- National Natural Science Foundation of China [81870082, 82070158, 81800191]
- Guangxi Natural Science Foundation Program [2019GXNSFDA245031]
- Dawn Program of Shanghai Education Commission [19SG14]
- Innovation Program of Shanghai Municipal Education Commission [YG2017MS31]
The study demonstrates that CDK9 inhibitors induce apoptosis in B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, providing a new therapeutic strategy for B-ALL treatment.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据