ArticleeLife2021
Intrinsic OXPHOS limitations underlie cellular bioenergetics in leukemia.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 53 citations in OpenAlex.
- Pharmacological blockade of rho kinase enhances venetoclax responses in translational models of acute myeloid leukemia.Haematologica · 2026Article
- Mitochondrial transfer in acute myeloid leukaemia and multiple myeloma: Mechanisms, consequences and potential therapeutic opportunities.The FEBS journal · 2026Review
- Article
- Myeloid differentiation-associated autophagy drives venetoclax resistance in AML.Research square · 2026Article
- Review
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Chemical-induced colitis lowers mitochondrial bioenergetic function in colonic tissue with minimal impacts on the proteome.Scientific reports · 2026Article
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- HER2-driven mammary tumorigenesis enhances bioenergetics despite reductions in mitochondrial content.eLife · 2026Article
- Intrinsic and niche-dependent metabolic regulation of haematopoietic stem cells and implications for leukaemogenesis.Nature cell biology · 2026Review
- Mitochondrial heteroplasmy is a risk factor for the development of chronic lymphocytic leukemia.Nature communications · 2026Article
- Chemical-induced colitis lowers mitochondrial bioenergetic function in the colonic epithelium with minimal impacts on the proteome.Research square · 2025Article
- Metabolomics of healthy hematopoietic stem cells and leukemic stem cells.Journal of clinical and translational research · 2025Article
- Impact of physiological media on acute myeloid leukemia bioenergetics and cell proliferation.Cancer & metabolism · 2025Article
- Mapping of Functional Metabolic Phenotypes in Acute Myeloid Leukemia.Cancer medicine · 2025Article
- Acute myeloid leukemia mitochondria hydrolyze ATP to support oxidative metabolism and resist chemotherapy.Science advances · 2025Article
- Altered metabolism in cancer: insights into energy pathways and therapeutic targets.Molecular cancer · 2024Review
- Harnessing Porphyrin Accumulation in Liver Cancer: Combining Genomic Data and Drug Targeting.Biomolecules · 2024Article
- Amino Acid and Glucose Fermentation Maintain ATP Content in Mouse and Human Malignant Glioma Cells.ASN neuro · 2024Article
- Mitochondrial abnormalities as a target of intervention in acute myeloid leukemia.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Currently there is great interest in targeting mitochondrial oxidative phosphorylation (OXPHOS) in cancer. However, notwithstanding the targeting of mutant dehydrogenases, nearly all hopeful 'mito-therapeutics' cannot discriminate cancerous from non-cancerous OXPHOS and thus suffer from a limited therapeutic index. Using acute myeloid leukemia (AML) as a model, herein, we leveraged an in-house diagnostic biochemical workflow to identify 'actionable' bioenergetic vulnerabilities intrinsic to cancerous mitochondria. Consistent with prior reports, AML growth and proliferation was associated with a hyper-metabolic phenotype which included increases in basal and maximal respiration. However, despite having nearly 2-fold more mitochondria per cell, clonally expanding hematopoietic stem cells, leukemic blasts, as well as chemoresistant AML were all consistently hallmarked by intrinsic OXPHOS limitations. Remarkably, by performing experiments across a physiological span of ATP free energy, we provide direct evidence that leukemic mitochondria are particularly poised to consume ATP. Relevant to AML biology, acute restoration of oxidative ATP synthesis proved highly cytotoxic to leukemic blasts, suggesting that active OXPHOS repression supports aggressive disease dissemination in AML. Together, these findings argue against ATP being the primary output of leukemic mitochondria and provide proof-of-principle that restoring, rather than disrupting, OXPHOS may represent an untapped therapeutic avenue for combatting hematological malignancy and chemoresistance.
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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.