ArticleScience advances2024
RIPK3 deficiency blocks R-2-hydroxyglutarate-induced necroptosis in IDH-mutated AML cells.
Article in Science advances, 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, 19 citations in OpenAlex.
- Necroptosis as a key player in cervical cancer progression and management: a systematic review and transcriptomic cross-study consensus analysis.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Dissecting PCD-driven molecular landscapes in AML: a multi-omic framework for prognostication and therapeutic targeting.Clinical and experimental medicine · 2026Article
- Osthole attenuates trastuzumab-induced cardiotoxicity in mice by enhancing autophagy via regulating the p38MAPK/mTOR signaling pathway.Journal of traditional and complementary medicine · 2026Article
- Leveraging Deep Learning to Construct a Programmed Cell Death-Driven Prognostic Signature in Acute Myeloid Leukemia.Current issues in molecular biology · 2026Article
- Aberrant methylation limits antitumoral inflammation in lung adenocarcinoma by restricting RIPK3 expression.Science advances · 2026Article
- Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.EXCLI journal · 2026Review
- Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review).Oncology reports · 2025Review
- Cracking the code of cancer immunotherapy resistance: emerging roles of pyroptosis and necroptosis.Journal of experimental & clinical cancer research : CR · 2025Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Advances in the regulation of macrophage polarization by the tumor microenvironment.Discover oncology · 2025Review
- Necroptosis in cancer: insight from epigenetic, post-transcriptional and post-translational modifications.Journal of hematology & oncology · 2025Review
- Cell death and cancer: Metabolic interconnections.Cell reports · 2025Review
- Optogenetically Activatable MLKL as a Standalone Functional Module for Necroptosis and Therapeutic Applications in Antitumoral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The molecular mechanisms, roles, and potential applications of PANoptosis in cancer treatment.Frontiers in immunology · 2025Review
- Prognostic Implications and Immune Landscape Analysis of Necroptosis-associated Gene Signatures in Acute Myeloid Leukemia.Journal of Cancer · 2025Article
- Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy.Frontiers in pharmacology · 2025Review
- Chemotherapy resistance in acute myeloid leukemia is mediated by A20 suppression of spontaneous necroptosis.Nature communications · 2024Article
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.
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Registered trials
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