A review on the emerging roles of pyruvate kinase M2 in anti-leukemia therapy

Guan Jun Yang; Jia Wu; Chung Hang Leung; Dik Lung Ma; Jiong Chen

doi:10.1016/j.ijbiomac.2021.10.213

A review on the emerging roles of pyruvate kinase M2 in anti-leukemia therapy

Guan Jun Yang, Jia Wu, Chung Hang Leung^*, Dik Lung Ma^*, Jiong Chen

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Review article › peer-review

17 Citations (Scopus)

Abstract

Glycolysis is an important step in respiration and provides energy for cellular processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, plays an important role in tumor cell metabolism and proliferation. It is also specifically overexpressed in leukemia cells and contributes to leukemic proliferation, differentiation, and drug resistance through both aerobic glycolysis and non-metabolic pathways. In this review, the functions and regulatory roles of PKM2 are firstly introduced. Then, the molecular mechanisms of PKM2 in leukemogenesis are summarized. Next, reported PKM2 modulators and their anti-leukemia mechanisms are described. Finally, the current challenges and the potential opportunities of PKM2 inhibitors or agonists in leukemia therapy are discussed.

Original language	English
Pages (from-to)	1499-1506
Number of pages	8
Journal	International Journal of Biological Macromolecules
Volume	193, Part B
DOIs	https://doi.org/10.1016/j.ijbiomac.2021.10.213
Publication status	Published - 15 Dec 2021

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Leukemia
Modulators
Pyruvate kinase M2

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10.1016/j.ijbiomac.2021.10.213

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abstract = "Glycolysis is an important step in respiration and provides energy for cellular processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, plays an important role in tumor cell metabolism and proliferation. It is also specifically overexpressed in leukemia cells and contributes to leukemic proliferation, differentiation, and drug resistance through both aerobic glycolysis and non-metabolic pathways. In this review, the functions and regulatory roles of PKM2 are firstly introduced. Then, the molecular mechanisms of PKM2 in leukemogenesis are summarized. Next, reported PKM2 modulators and their anti-leukemia mechanisms are described. Finally, the current challenges and the potential opportunities of PKM2 inhibitors or agonists in leukemia therapy are discussed.",

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note = "Funding Information: This work is supported by the Natural Science Foundation of Zhejiang Province ( LZ18C190001 ), National Natural Science Foundation of China ( 31972821 ) and State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products ( 2010DS700124-ZZ2008 ), the General Scientific Research Project of Education of Zhejiang Province ( Y202147351 ), the Starting Research Fund of Ningbo University ( 421912073 ), the Science and Technology Development Fund , Macau SAR (File no. 0007/2020/A1 ), SKL-QRCM(UM)-2020-2022, and the University of Macau ( MYRG2019-00002-ICMS ). Hong Kong Baptist University , the Health and Medical Research Fund ( HMRF/14150561 ), the National Natural Science Foundation of China ( 22077109 and 21775131 ) Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

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AU - Yang, Guan Jun

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AU - Chen, Jiong

N1 - Funding Information: This work is supported by the Natural Science Foundation of Zhejiang Province ( LZ18C190001 ), National Natural Science Foundation of China ( 31972821 ) and State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products ( 2010DS700124-ZZ2008 ), the General Scientific Research Project of Education of Zhejiang Province ( Y202147351 ), the Starting Research Fund of Ningbo University ( 421912073 ), the Science and Technology Development Fund , Macau SAR (File no. 0007/2020/A1 ), SKL-QRCM(UM)-2020-2022, and the University of Macau ( MYRG2019-00002-ICMS ). Hong Kong Baptist University , the Health and Medical Research Fund ( HMRF/14150561 ), the National Natural Science Foundation of China ( 22077109 and 21775131 ) Publisher Copyright: © 2021 Elsevier B.V.

PY - 2021/12/15

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N2 - Glycolysis is an important step in respiration and provides energy for cellular processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, plays an important role in tumor cell metabolism and proliferation. It is also specifically overexpressed in leukemia cells and contributes to leukemic proliferation, differentiation, and drug resistance through both aerobic glycolysis and non-metabolic pathways. In this review, the functions and regulatory roles of PKM2 are firstly introduced. Then, the molecular mechanisms of PKM2 in leukemogenesis are summarized. Next, reported PKM2 modulators and their anti-leukemia mechanisms are described. Finally, the current challenges and the potential opportunities of PKM2 inhibitors or agonists in leukemia therapy are discussed.

AB - Glycolysis is an important step in respiration and provides energy for cellular processes. Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, plays an important role in tumor cell metabolism and proliferation. It is also specifically overexpressed in leukemia cells and contributes to leukemic proliferation, differentiation, and drug resistance through both aerobic glycolysis and non-metabolic pathways. In this review, the functions and regulatory roles of PKM2 are firstly introduced. Then, the molecular mechanisms of PKM2 in leukemogenesis are summarized. Next, reported PKM2 modulators and their anti-leukemia mechanisms are described. Finally, the current challenges and the potential opportunities of PKM2 inhibitors or agonists in leukemia therapy are discussed.

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A review on the emerging roles of pyruvate kinase M2 in anti-leukemia therapy

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