ArticleNature cancer2021
Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 109 citations in OpenAlex.
- Results of a phase 1 trial testing ruxolitinib plus venetoclax in patients with relapsed/refractory acute myeloid leukemia.Blood neoplasia · 2026Trial
- Non-genetic remodeling drives leukemia propagation and reveals actionable vulnerabilities in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Venetoclax and hypomethylating agents synergize to increase cell death and metabolic remodeling in acute B-lymphoblastic leukemia cells.Molecular metabolism · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Biomimetic Copper-Doped Nano-Aluminum Adjuvant Potentiates Therapy in Chemoresistant Acute Myeloid Leukemia.Advanced healthcare materials · 2026Article
- Advancing precision therapy in pediatric acute myeloid leukemia through PDX models and mitochondrial targeting.Blood advances · 2026Article
- Glutaredoxin 2 is essential for AML survival through mitochondrial permeability transition pore regulation.Blood · 2026Article
- Succinate receptor 1 restricts hematopoiesis and prevents acute myeloid leukemia progression.Nature communications · 2026Article
- Caffeic acid phenethyl ester induced apoptosis in chronic myeloid leukemia cells by inhibiting mitochondrial complex I.Scientific reports · 2026Article
- Tumor metabolic plasticity in therapy resistance: from the Warburg effect to mitochondrial hijacking.Theranostics · 2026Review
- Adaptation of redox metabolism in drug-tolerant persister cells is a vulnerability to prevent relapse in pancreatic cancer.Oncogenesis · 2025Article
- DDX6 undergoes phase separation to modulate metabolic plasticity and chemoresistance.Nature communications · 2025Article
- G-quadruplex ligand RHPS4 compromises cellular radioresistance by inhibiting the mitochondrial adaptive response induced by ionizing irradiation.NAR cancer · 2025Article
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Genes-first and phenotypes-first paths to treatment resistance in hematological malignancies.Cell death & disease · 2025Review
- Pitavastatin counteracts venetoclax resistance mechanisms in acute myeloid leukemia by depleting geranylgeranyl pyrophosphate.bioRxiv : the preprint server for biology · 2025Article
- Small-molecule OPA1 inhibitors reverse mitochondrial adaptations to overcome therapy resistance in acute myeloid leukemia.Science advances · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapy resistance represents a major clinical challenge in acute myeloid leukemia (AML). Here we define a 'MitoScore' signature, which identifies high mitochondrial oxidative phosphorylation in vivo and in patients with AML. Primary AML cells with cytarabine (AraC) resistance and a high MitoScore relied on mitochondrial Bcl2 and were highly sensitive to venetoclax (VEN) + AraC (but not to VEN + azacytidine). Single-cell transcriptomics of VEN + AraC-residual cell populations revealed adaptive resistance associated with changes in oxidative phosphorylation, electron transport chain complex and the TP53 pathway. Accordingly, treatment of VEN + AraC-resistant AML cells with electron transport chain complex inhibitors, pyruvate dehydrogenase inhibitors or mitochondrial ClpP protease agonists substantially delayed relapse following VEN + AraC. These findings highlight the central role of mitochondrial adaptation during AML therapy and provide a scientific rationale for alternating VEN + azacytidine with VEN + AraC in patients with a high MitoScore and to target mitochondrial metabolism to enhance the sensitivity of AML cells to currently approved therapies.
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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.