ArticleJCI insight2022
Somatic gene mutations expose cytoplasmic DNA to co-opt the cGAS/STING/NLRP3 axis in myelodysplastic syndromes.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Role of the STING pathway in myeloid neoplasms: a prospero-registered systematic review of principal hurdles of STING on the road to the clinical practice.Medical oncology (Northwood, London, England) · 2024Pooled it
- TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases.Journal of advanced research · 2026Article
- TET2 loss enhances early response to inflammation in primitive and committed myeloid cells.Experimental hematology · 2026Article
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- Vulnerability of SRSF2-mutated chronic myelomonocytic leukemia to perturbation of the cGAS-STING pathway.Blood advances · 2026Article
- From Germline Susceptibility to Therapeutic Vulnerability: DNA Damage Response Gene Mutations Driving Multiple Myeloma Evolution and Precision Therapy.Human mutation · 2026Review
- asxl1 C-terminal truncation and SRSF2 mutation drive leukemogenesis via immune reprogramming.Leukemia · 2025Article
- NLRP3-induced systemic inflammation controls the development of JAK2V617F mutant myeloproliferative neoplasms.Nature communications · 2025Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
- Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis.Journal of translational autoimmunity · 2025Article
- Research and progress of cGAS/STING/NLRP3 signaling pathway: a mini review.Frontiers in immunology · 2025Review
- Implications for metabolic disturbances in myelodysplastic syndromes.Seminars in hematology · 2024Review
- Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.Molecular cancer · 2024Review
- The 4EHP-mediated translational repression of cGAS impedes the host immune response against DNA viruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Heat Stroke Induces Pyroptosis in Spermatogonia via the cGAS-STING Signaling Pathway.Physiological research · 2024Article
- Nucleic acid-induced inflammation on hematopoietic stem cells.Experimental hematology · 2024Article
- cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis.International journal of molecular sciences · 2024Review
- cGAS-STING, inflammasomes and pyroptosis: an overview of crosstalk mechanism of activation and regulation.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
NLRP3 inflammasome and IFN-stimulated gene (ISG) induction are key biological drivers of ineffective hematopoiesis and inflammation in myelodysplastic syndromes (MDSs). Gene mutations involving mRNA splicing and epigenetic regulatory pathways induce inflammasome activation and myeloid lineage skewing in MDSs through undefined mechanisms. Using immortalized murine hematopoietic stem and progenitor cells harboring these somatic gene mutations and primary MDS BM specimens, we showed accumulation of unresolved R-loops and micronuclei with concurrent activation of the cytosolic sensor cyclic GMP-AMP synthase. Cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling caused ISG induction, NLRP3 inflammasome activation, and maturation of the effector protease caspase-1. Deregulation of RNA polymerase III drove cytosolic R-loop generation, which upon inhibition, extinguished ISG and inflammasome response. Mechanistically, caspase-1 degraded the master erythroid transcription factor, GATA binding protein 1, provoking anemia and myeloid lineage bias that was reversed by cGAS inhibition in vitro and in Tet2-/- hematopoietic stem and progenitor cell-transplanted mice. Together, these data identified a mechanism by which functionally distinct mutations converged upon the cGAS/STING/NLRP3 axis in MDS, directing ISG induction, pyroptosis, and myeloid lineage skewing.
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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.