ArticleBritish journal of haematology2019
SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation.
Article in British journal of haematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- SRSF2 mutations drive daunorubicin resistance in acute myeloid leukemia via THBS1 stabilization.Journal of experimental & clinical cancer research : CR · 2026Article
- The role of telomeres in leukemic stem cells function.Regenerative therapy · 2025Review
- Deciphering the molecular landscape of acute myeloid leukemia initiation and relapse: a systems biology approach.Medical oncology (Northwood, London, England) · 2025Review
- Review
- SIRT1 as a masterful reciprocal regulator of molecular mechanisms and signaling pathways involved in tumor growth and expansion.Clinical and experimental medicine · 2025Review
- The role and mechanism of fatty acid oxidation in cancer drug resistance.Cell death discovery · 2025Review
- The Role of the Sirtuin Family Histone Deacetylases in Acute Myeloid Leukemia-A Promising Road Ahead.Cancers · 2025Review
- Metabolic dependencies of acute myeloid leukemia stem cells.International journal of hematology · 2024Review
- Application of omics in the diagnosis, prognosis, and treatment of acute myeloid leukemia.Biomarker research · 2024Review
- Supplementing Boar Diet with Nicotinamide Mononucleotide Improves Sperm Quality Probably through the Activation of the SIRT3 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Mitochondrial sirtuins: Energy dynamics and cancer metabolism.Molecules and cells · 2024Review
- Reactive oxygen species and its role in pathogenesis and resistance to therapy in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Bidirectional interplay between metabolism and epigenetics in hematopoietic stem cells and leukemia.The EMBO journal · 2023Review
- Evaluation of ARK5 and SIRT3 expression in renal cell carcinoma and their clinical significance.Diagnostic pathology · 2023Article
- Simultaneous inhibition of Sirtuin 3 and cholesterol homeostasis targets acute myeloid leukemia stem cells by perturbing fatty acid β-oxidation and inducing lipotoxicity.Haematologica · 2023Article
- Disruption of mitochondrial oxidative phosphorylation by chidamide eradicates leukemic cells in AML.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Succinate-Directed Approaches for Warburg Effect-Targeted Cancer Management, an Alternative to Current Treatments?Cancers · 2023Review
- Chemotherapeutic Activity of Pitavastatin in Vincristine Resistant B-Cell Acute Lymphoblastic Leukemia.Cancers · 2023Article
- Plant-derived extracts and metabolic modulation in leukemia: a promising approach to overcome treatment resistance.Frontiers in molecular biosciences · 2023Review
- Targeting metabolic vulnerabilities to overcome resistance to therapy in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
Corrections and comments
- Erratum issuedCorrigendum.2020
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukaemia (AML) cells possess metabolism profiles, such as higher rates of oxidative phosphorylation and dependence on fatty acid oxidation for survival, and are dependent on the sophisticated regulation of reactive oxygen species (ROS) generation for survival, drug resistance and stemness maintenance. We found that sensitivity of primary AML cells to cytarabine correlated with SOD2 acetylation and the ability of the drug to induce mitochondrial ROS. The SOD2 deacetylase, SIRT3, protected AML cells from chemotherapy as shown by inhibited apoptosis via inhibited drug-induced production of mitochondrial ROS. SIRT3 significantly decreased nicotinamide adenine dinucleotide phosphate (NADP)/reduced NADP ratio and increased reduced glutathione/oxidized glutathione ratio. Furthermore, SIRT3 enhanced oxidative phosphorylation (OxPhos) in AML cells under both basic and cytarabine-treated conditions. A xenograft mouse model showed that SIRT3 overexpressing AML cells and patient-derived xenograft mice bearing high SIRT3 deacetylase activity were more resistant to chemotherapy in vivo. SIRT3 inhibitor displayed synergy with cytarabine to ablate AML cells in vitro and in mouse models. Taken together, our study showed that SIRT3 is capable of reprograming mitochondrial metabolism towards OxPhos and downregulating ROS generation, which contribute to the chemoresistance of AML cells. SIRT3 can be utilized as a potential therapeutic target to improve the anti-leukaemic efficacy of standard chemotherapeutic agents for AML.
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