Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells
Despite intensive chemotherapy regimens, up to 60% of adults with acute myeloid leukaemia (AML) will relapse and eventually succumb to their disease. Recent studies suggest that leukaemic stem cells (LSCs) drive AML relapse by residing in the bone marrow niche and adapting their metabolic profile. M...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.807266/full |
| _version_ | 1818897738867146752 |
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| author | Yashar Mesbahi Yashar Mesbahi Yashar Mesbahi Toby N. Trahair Toby N. Trahair Toby N. Trahair Richard B. Lock Richard B. Lock Richard B. Lock Patrick Connerty Patrick Connerty Patrick Connerty |
| author_facet | Yashar Mesbahi Yashar Mesbahi Yashar Mesbahi Toby N. Trahair Toby N. Trahair Toby N. Trahair Richard B. Lock Richard B. Lock Richard B. Lock Patrick Connerty Patrick Connerty Patrick Connerty |
| author_sort | Yashar Mesbahi |
| collection | DOAJ |
| description | Despite intensive chemotherapy regimens, up to 60% of adults with acute myeloid leukaemia (AML) will relapse and eventually succumb to their disease. Recent studies suggest that leukaemic stem cells (LSCs) drive AML relapse by residing in the bone marrow niche and adapting their metabolic profile. Metabolic adaptation and LSC plasticity are novel hallmarks of leukemogenesis that provide important biological processes required for tumour initiation, progression and therapeutic responses. These findings highlight the importance of targeting metabolic pathways in leukaemia biology which might serve as the Achilles’ heel for the treatment of AML relapse. In this review, we highlight the metabolic differences between normal haematopoietic cells, bulk AML cells and LSCs. Specifically, we focus on four major metabolic pathways dysregulated in AML; (i) glycolysis; (ii) mitochondrial metabolism; (iii) amino acid metabolism; and (iv) lipid metabolism. We then outline established and emerging drug interventions that exploit metabolic dependencies of leukaemic cells in the treatment of AML. The metabolic signature of AML cells alters during different biological conditions such as chemotherapy and quiescence. Therefore, targeting the metabolic vulnerabilities of these cells might selectively eradicate them and improve the overall survival of patients with AML. |
| first_indexed | 2024-12-19T19:20:57Z |
| format | Article |
| id | doaj.art-9117b56c6d904ca5a331ca3027662682 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T19:20:57Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-9117b56c6d904ca5a331ca30276626822022-12-21T20:09:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.807266807266Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem CellsYashar Mesbahi0Yashar Mesbahi1Yashar Mesbahi2Toby N. Trahair3Toby N. Trahair4Toby N. Trahair5Richard B. Lock6Richard B. Lock7Richard B. Lock8Patrick Connerty9Patrick Connerty10Patrick Connerty11Children’s Cancer Institute, Lowy Cancer Centre, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaSchool of Women’s and Children’s Health, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaUniversity of New South Wales Centre for Childhood Cancer Research, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaChildren’s Cancer Institute, Lowy Cancer Centre, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaSchool of Women’s and Children’s Health, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaKids Cancer Centre, Sydney Children’s Hospital, Randwick, NSW, AustraliaChildren’s Cancer Institute, Lowy Cancer Centre, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaSchool of Women’s and Children’s Health, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaUniversity of New South Wales Centre for Childhood Cancer Research, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaChildren’s Cancer Institute, Lowy Cancer Centre, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaSchool of Women’s and Children’s Health, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaUniversity of New South Wales Centre for Childhood Cancer Research, University of New South Wales (UNSW) Sydney, Kensington, NSW, AustraliaDespite intensive chemotherapy regimens, up to 60% of adults with acute myeloid leukaemia (AML) will relapse and eventually succumb to their disease. Recent studies suggest that leukaemic stem cells (LSCs) drive AML relapse by residing in the bone marrow niche and adapting their metabolic profile. Metabolic adaptation and LSC plasticity are novel hallmarks of leukemogenesis that provide important biological processes required for tumour initiation, progression and therapeutic responses. These findings highlight the importance of targeting metabolic pathways in leukaemia biology which might serve as the Achilles’ heel for the treatment of AML relapse. In this review, we highlight the metabolic differences between normal haematopoietic cells, bulk AML cells and LSCs. Specifically, we focus on four major metabolic pathways dysregulated in AML; (i) glycolysis; (ii) mitochondrial metabolism; (iii) amino acid metabolism; and (iv) lipid metabolism. We then outline established and emerging drug interventions that exploit metabolic dependencies of leukaemic cells in the treatment of AML. The metabolic signature of AML cells alters during different biological conditions such as chemotherapy and quiescence. Therefore, targeting the metabolic vulnerabilities of these cells might selectively eradicate them and improve the overall survival of patients with AML.https://www.frontiersin.org/articles/10.3389/fonc.2022.807266/fullacute myeloid leukaemiametabolic plasticityleukaemic stem cellscancer metabolismmetabolic targeting |
| spellingShingle | Yashar Mesbahi Yashar Mesbahi Yashar Mesbahi Toby N. Trahair Toby N. Trahair Toby N. Trahair Richard B. Lock Richard B. Lock Richard B. Lock Patrick Connerty Patrick Connerty Patrick Connerty Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells Frontiers in Oncology acute myeloid leukaemia metabolic plasticity leukaemic stem cells cancer metabolism metabolic targeting |
| title | Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells |
| title_full | Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells |
| title_fullStr | Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells |
| title_full_unstemmed | Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells |
| title_short | Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells |
| title_sort | exploring the metabolic landscape of aml from haematopoietic stem cells to myeloblasts and leukaemic stem cells |
| topic | acute myeloid leukaemia metabolic plasticity leukaemic stem cells cancer metabolism metabolic targeting |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.807266/full |
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