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Targeting metabolic reprogramming in chronic lymphocytic leukemia

Metabolic 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 c...

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Autores principales: Nie, Yu, Yun, Xiaoya, Zhang, Ya, Wang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235173/
https://www.ncbi.nlm.nih.gov/pubmed/35761419
http://dx.doi.org/10.1186/s40164-022-00292-z
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author Nie, Yu
Yun, Xiaoya
Zhang, Ya
Wang, Xin
author_facet Nie, Yu
Yun, Xiaoya
Zhang, Ya
Wang, Xin
author_sort Nie, Yu
collection PubMed
description Metabolic 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.
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spelling pubmed-92351732022-06-28 Targeting metabolic reprogramming in chronic lymphocytic leukemia Nie, Yu Yun, Xiaoya Zhang, Ya Wang, Xin Exp Hematol Oncol Review Metabolic 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. BioMed Central 2022-06-27 /pmc/articles/PMC9235173/ /pubmed/35761419 http://dx.doi.org/10.1186/s40164-022-00292-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Nie, Yu
Yun, Xiaoya
Zhang, Ya
Wang, Xin
Targeting metabolic reprogramming in chronic lymphocytic leukemia
title Targeting metabolic reprogramming in chronic lymphocytic leukemia
title_full Targeting metabolic reprogramming in chronic lymphocytic leukemia
title_fullStr Targeting metabolic reprogramming in chronic lymphocytic leukemia
title_full_unstemmed Targeting metabolic reprogramming in chronic lymphocytic leukemia
title_short Targeting metabolic reprogramming in chronic lymphocytic leukemia
title_sort targeting metabolic reprogramming in chronic lymphocytic leukemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235173/
https://www.ncbi.nlm.nih.gov/pubmed/35761419
http://dx.doi.org/10.1186/s40164-022-00292-z
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