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

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 ef...

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Autores principales: Huang, Wen-Li, Abudureheman, Tuersunayi, Xia, Jing, Chu, Lei, Zhou, Hang, Zheng, Wei-Wei, Zhou, Neng, Shi, Rong-Yi, Li, Ming-Hao, Zhu, Jian-Min, Qing, Kai, Ji, Chao, Liang, Kai-Wei, Guo, Sa, Yin, Gang, Duan, Cai-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969802/
https://www.ncbi.nlm.nih.gov/pubmed/33748130
http://dx.doi.org/10.3389/fcell.2021.641271
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author Huang, Wen-Li
Abudureheman, Tuersunayi
Xia, Jing
Chu, Lei
Zhou, Hang
Zheng, Wei-Wei
Zhou, Neng
Shi, Rong-Yi
Li, Ming-Hao
Zhu, Jian-Min
Qing, Kai
Ji, Chao
Liang, Kai-Wei
Guo, Sa
Yin, Gang
Duan, Cai-Wen
author_facet Huang, Wen-Li
Abudureheman, Tuersunayi
Xia, Jing
Chu, Lei
Zhou, Hang
Zheng, Wei-Wei
Zhou, Neng
Shi, Rong-Yi
Li, Ming-Hao
Zhu, Jian-Min
Qing, Kai
Ji, Chao
Liang, Kai-Wei
Guo, Sa
Yin, Gang
Duan, Cai-Wen
author_sort Huang, Wen-Li
collection PubMed
description 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.
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spelling pubmed-79698022021-03-19 CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism Huang, Wen-Li Abudureheman, Tuersunayi Xia, Jing Chu, Lei Zhou, Hang Zheng, Wei-Wei Zhou, Neng Shi, Rong-Yi Li, Ming-Hao Zhu, Jian-Min Qing, Kai Ji, Chao Liang, Kai-Wei Guo, Sa Yin, Gang Duan, Cai-Wen Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7969802/ /pubmed/33748130 http://dx.doi.org/10.3389/fcell.2021.641271 Text en Copyright © 2021 Huang, Abudureheman, Xia, Chu, Zhou, Zheng, Zhou, Shi, Li, Zhu, Qing, Ji, Liang, Guo, Yin and Duan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Huang, Wen-Li
Abudureheman, Tuersunayi
Xia, Jing
Chu, Lei
Zhou, Hang
Zheng, Wei-Wei
Zhou, Neng
Shi, Rong-Yi
Li, Ming-Hao
Zhu, Jian-Min
Qing, Kai
Ji, Chao
Liang, Kai-Wei
Guo, Sa
Yin, Gang
Duan, Cai-Wen
CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title_full CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title_fullStr CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title_full_unstemmed CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title_short CDK9 Inhibitor Induces the Apoptosis of B-Cell Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolytic Metabolism
title_sort cdk9 inhibitor induces the apoptosis of b-cell acute lymphocytic leukemia by inhibiting c-myc-mediated glycolytic metabolism
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969802/
https://www.ncbi.nlm.nih.gov/pubmed/33748130
http://dx.doi.org/10.3389/fcell.2021.641271
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