ArticleCancer discovery2023
(R)-2-Hydroxyglutarate Inhibits KDM5 Histone Lysine Demethylases to Drive Transformation in IDH-Mutant Cancers.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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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Who cites it
41 citing papers in PubMed, 39 citations in OpenAlex.
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- TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy.Cell biochemistry and function · 2026Review
- DNA Methylation Stochasticity Is Linked to Transcriptional Variability and Convergent Epigenetic Disruption across Genetic Subtypes of Acute Myeloid Leukemia.Cancer research · 2026Article
- Chronic stress and cancer progression through neuro‑endocrine‑immune networks (Review).Oncology reports · 2026Review
- Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells.Nature chemical biology · 2026Article
- Integrating MRI radiomics and transcriptomics to predict IDH mutation status and prognosis in glioma.Cancer cell international · 2026Article
- Dual inhibition of KDM4B and KDM5A disassembles the PAX3-FOXO1 transcriptional program in fusion-positive rhabdomyosarcoma.Biology direct · 2026Article
- l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression.The Journal of clinical investigation · 2026Article
- Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Mutant Isocitrate Dehydrogenase 1 Sensitizes Intrahepatic Cholangiocarcinoma Cells to MDM2 Inhibitors.Cancer research communications · 2026Article
- Prickle4 Drives Microenvironmental Remodeling and Resistance to Parp Inhibition in IDH-Mutant Glioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.Cell death & disease · 2025Article
- Hypoxia Induces Immunosuppression by Silencing STING in Cancer.Cancer research · 2025Article
- Profiling Inhibitor Scaffolds for the Cancer Target Jumonji-C Domain-Containing Protein 6.ChemMedChem · 2025Article
- State of the art: glioma-associated epilepsy-bridging tumor biology and epileptogenesis.Neurological research and practice · 2025Review
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- Integrative machine learning reveals the biological function and prognostic significance of α-ketoglutarate in gastric cancer.Oncology letters · 2025Article
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 2 countries.
Funding
Abstract
Oncogenic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in a wide range of cancers, including acute myeloid leukemia (AML) and glioma. Mutant IDH enzymes convert 2-oxoglutarate (2OG) to (R)-2-hydroxyglutarate [(R)-2HG], an oncometabolite that is hypothesized to promote cellular transformation by dysregulating 2OG-dependent enzymes. The only (R)-2HG target that has been convincingly shown to contribute to transformation by mutant IDH is the myeloid tumor suppressor TET2. However, there is ample evidence to suggest that (R)-2HG has other functionally relevant targets in IDH-mutant cancers. Here, we show that (R)-2HG inhibits KDM5 histone lysine demethylases and that this inhibition contributes to cellular transformation in IDH-mutant AML and IDH-mutant glioma. These studies provide the first evidence of a functional link between dysregulation of histone lysine methylation and transformation in IDH-mutant cancers. SIGNIFICANCE: Mutant IDH is known to induce histone hypermethylation. However, it is not known if this hypermethylation is functionally significant or is a bystander effect of (R)-2HG accumulation in IDH-mutant cells. Here, we provide evidence that KDM5 inhibition by (R)-2HG contributes to mutant IDH-mediated transformation in AML and glioma. This article is highlighted in the In This Issue feature, p. 1275.
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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.