Author:
Nie Yu,Yun Xiaoya,Zhang Ya,Wang Xin
Abstract
AbstractMetabolic reprogramming, fundamentally pivotal in carcinogenesis and progression of cancer, is considered as a promising therapeutic target against tumors. In chronic lymphocytic leukemia (CLL) cells, metabolic abnormalities mediate alternations in proliferation and survival compared with normal B cells. However, the role of metabolic reprogramming is still under investigation in CLL. In this review, the critical metabolic processes of CLL were summarized, particularly glycolysis, lipid metabolism and oxidative phosphorylation. The effects of T cells and stromal cells in the microenvironment on metabolism of CLL were also elucidated. Besides, the metabolic alternation is regulated by some oncogenes and tumor suppressor regulators, especially TP53, MYC and ATM. Thus, the agents targeting metabolic enzymes or signal pathways may impede the progression of CLL. Both the inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) statins and the lipoprotein lipase inhibitor orlistat induce the apoptosis of CLL cells. In addition, a series of oxidative phosphorylation inhibitors play important roles in decreasing the proliferation of CLL cells. We epitomized recent advancements in metabolic reprogramming in CLL and discussed their clinical potentiality for innovative therapy options. Metabolic reprogramming plays a vital role in the initiation and progression of CLL. Therapeutic approaches targeting metabolism have their advantages in improving the survival of CLL patients. This review may shed novel light on the metabolism of CLL, leading to the development of targeted agents based on the reshaping metabolism of CLL cells.
Funder
National Natural Science Foundation
Taishan Scholars Program of Shandong Province
Shandong Provincial Natural Science Foundation
Technology Development Project of Jinan City
Academic Promotion Programme of Shandong First Medical University
Shandong Provincial Hospital Youth Talent Plan
Key Research and Development Program of Shandong Province
Translational Research Grant of NCRCH
Shandong Provincial Engineering Research Center of Lymphoma
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology
Cited by
13 articles.
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