Cargando…
Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia
While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse i...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727299/ https://www.ncbi.nlm.nih.gov/pubmed/34561557 http://dx.doi.org/10.1038/s41375-021-01416-w |
_version_ | 1784626493162258432 |
---|---|
author | de Beauchamp, Lucie Himonas, Ekaterini Helgason, G. Vignir |
author_facet | de Beauchamp, Lucie Himonas, Ekaterini Helgason, G. Vignir |
author_sort | de Beauchamp, Lucie |
collection | PubMed |
description | While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells are still not eradicated with current treatments, due to various mechanisms that may contribute to therapy resistance, including cellular metabolic adaptations. In fact, recent studies have shown that LSCs and treatment-resistant cells are dependent on mitochondrial metabolism, hence rendering them sensitive to inhibition of mitochondrial oxidative phosphorylation (OXPHOS). As a result, rewired energy metabolism in leukaemic cells is now considered an attractive therapeutic target and the significance of this process is increasingly being recognised in various haematological malignancies. Therefore, identifying and targeting aberrant metabolism in drug-resistant leukaemic cells is an imperative and a relevant strategy for the development of new therapeutic options in leukaemia. In this review, we present a detailed overview of the most recent studies that present experimental evidence on how leukaemic cells can metabolically rewire, more specifically the importance of OXPHOS in LSCs and treatment-resistant cells, and the current drugs available to target this process. We highlight that uncovering specific energy metabolism dependencies will guide the identification of new and more targeted therapeutic strategies for myeloid leukaemia. |
format | Online Article Text |
id | pubmed-8727299 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-87272992022-01-18 Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia de Beauchamp, Lucie Himonas, Ekaterini Helgason, G. Vignir Leukemia Review Article While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells are still not eradicated with current treatments, due to various mechanisms that may contribute to therapy resistance, including cellular metabolic adaptations. In fact, recent studies have shown that LSCs and treatment-resistant cells are dependent on mitochondrial metabolism, hence rendering them sensitive to inhibition of mitochondrial oxidative phosphorylation (OXPHOS). As a result, rewired energy metabolism in leukaemic cells is now considered an attractive therapeutic target and the significance of this process is increasingly being recognised in various haematological malignancies. Therefore, identifying and targeting aberrant metabolism in drug-resistant leukaemic cells is an imperative and a relevant strategy for the development of new therapeutic options in leukaemia. In this review, we present a detailed overview of the most recent studies that present experimental evidence on how leukaemic cells can metabolically rewire, more specifically the importance of OXPHOS in LSCs and treatment-resistant cells, and the current drugs available to target this process. We highlight that uncovering specific energy metabolism dependencies will guide the identification of new and more targeted therapeutic strategies for myeloid leukaemia. Nature Publishing Group UK 2021-09-24 2022 /pmc/articles/PMC8727299/ /pubmed/34561557 http://dx.doi.org/10.1038/s41375-021-01416-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article de Beauchamp, Lucie Himonas, Ekaterini Helgason, G. Vignir Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title | Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title_full | Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title_fullStr | Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title_full_unstemmed | Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title_short | Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
title_sort | mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727299/ https://www.ncbi.nlm.nih.gov/pubmed/34561557 http://dx.doi.org/10.1038/s41375-021-01416-w |
work_keys_str_mv | AT debeauchamplucie mitochondrialmetabolismasapotentialtherapeutictargetinmyeloidleukaemia AT himonasekaterini mitochondrialmetabolismasapotentialtherapeutictargetinmyeloidleukaemia AT helgasongvignir mitochondrialmetabolismasapotentialtherapeutictargetinmyeloidleukaemia |