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

Int J Biol Macromol. 2021 Dec 15;193(Pt B):1499-1506. doi: 10.1016/j.ijbiomac.2021.10.213. Epub 2021 Nov 2.

Authors

Guan-Jun Yang¹, Jia Wu², Chung-Hang Leung³, Dik-Lung Ma⁴, Jiong Chen⁵

Affiliations

¹ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, Zhejiang, China; Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo 315211, China; Key Laboratory of Applied Marine Biotechnology of Ministry of Education, Ningbo University, Ningbo, 315211, China.
² Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China.
³ Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China; Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, 999078, Macao SAR, China. Electronic address: duncanleung@um.edu.mo.
⁴ Department of Chemistry, Hong Kong Baptist University, Kowloon 999077, Hong Kong, China. Electronic address: edmondma@hkbu.edu.hk.
⁵ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, Zhejiang, China; Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China; Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo 315211, China. Electronic address: jchen1975@163.com.

PMID: 34740687
DOI: 10.1016/j.ijbiomac.2021.10.213

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.

Keywords: Leukemia; Modulators; Pyruvate kinase M2.

Publication types

Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Glycolysis / drug effects
Humans
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / metabolism*
Pyruvate Kinase / metabolism*

Substances

Antineoplastic Agents
Pyruvate Kinase