ArticleNature communications2024
Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Characterizing gene perturbations in single cells via network divergence analysis.Nature communications · 2026Article
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Altered Expression of Mitochondrial Succinate Dehydrogenase Subunit D Influences Breast Cancer Progression.International journal of molecular sciences · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Succinate-mediated SUCNR1 activation in tumor-associated macrophages promotes M2 polarization and cetuximab resistance in colorectal cancer: in vitro and in vivo insights.Apoptosis : an international journal on programmed cell death · 2026Article
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Mitochondrial Dysfunction in Apoptosis-Resistant Acute Myeloid Leukemia Cells During a Sterile Inflammatory Response.Biomolecules · 2025Article
- Targeting mitochondrial dysfunction to intervene in liver cancer.Cancer biology & medicine · 2025Review
- Review
- SDH defective cancers: molecular mechanisms and treatment strategies.Cell biology and toxicology · 2025Review
- Nanomedicines Targeting Metabolic Pathways in the Tumor Microenvironment: Future Perspectives and the Role of AI.Metabolites · 2025Review
- Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance is vital for the poor prognosis of acute myeloid leukemia (AML) patients, but the underlying mechanism remains poorly understood. Given the unique microenvironment of bone marrow, we reasoned that drug resistance of AML might rely on distinct metabolic processes. Here, we identify succinate dehydrogenase (SDH) deficiency and over-cumulative succinate as typical features in AML, with a marked function in causing the resistance of AML cells to various anti-cancer therapies. Mechanistically, succinate promotes the accumulation of oncogenic proteins in a manner that precedes transcriptional activation. This function is mediated by succinate-triggered upregulation of ubiquitin-conjugating enzyme E2M (UBC12) phosphorylation, which impairs its E2 function in cullins neddylation. Notably, decreasing succinate by fludarabine can restore the sensitivity of anti-cancer drugs in SDH-deficient AML. Together, we uncover the function of succinate in driving drug resistance by regulating p-UBC12/cullin activity, and indicate reshaping succinate metabolism as a promising treatment for SDH-deficient AML.
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