ArticleNature communications2023
Pyruvate anaplerosis is a targetable vulnerability in persistent leukaemic stem cells.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Mitochondrial DNA mutations are associated with impaired oxidative phosphorylation and enhanced imatinib response in chronic myeloid leukemia.HemaSphere · 2026Article
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.Cancers · 2026Review
- FBXO3-mediated DUSP9 ubiquitination promotes leukemia stem cell maintenance and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell reports. Medicine · 2026Article
- Methods and Guidelines for Metabolism Studies: Applications to Cancer Research.International journal of molecular sciences · 2025Review
- In silico development and validation of a novel six-gene-derived signature in hepatocellular carcinoma.Translational cancer research · 2025Article
- Review
- Targeting DDX3X eliminates leukemia stem cells in chronic myeloid leukemia by blocking NT5DC2 mRNA translation.Oncogene · 2025Article
- Tyrosine Kinase Inhibitor Therapy Enhances Stem Cells Profile and May Contribute to Survival of Chronic Myeloid Leukemiastem Cells.Journal of clinical medicine · 2025Article
- Dietary nutrient intake and cancer presence: evidence from a cross-sectional study.Frontiers in nutrition · 2025Article
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Targeting Translation and the Cell Cycle Inversely Affects CTC Metabolism but Not Metastasis.Cancers · 2023Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Deregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.