ArticleNature medicine2018
Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 45 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia: a Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study
The Efficacy and Safety of Thalidomide Combined With Low-dose Hormones in the Treatment of Severe New Coronavirus (COVID-19) Pneumonia: a Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study
Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- Single-cell profiling of natural killer/T-cell lymphoma reveals stratified immune features and potential therapeutic implications.Nature communications · 2026Article
- The prognostic predictive SER model for NK/T-cell lymphoma in the era of modern immunotherapy.Cancer cell international · 2026Article
- Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic lymphohistiocytosis-a Rare and Dangerous Disease.Blood and lymphatic cancer : targets and therapy · 2026Review
- Peripheral blood immune profiling reveals key signatures in newly diagnosed NK/T cell lymphoma patients.Theranostics · 2026Article
- Epstein-Barr virus-associated tumors: commonalities in pathogenesis and the tumor immune microenvironment.Frontiers in immunology · 2026Review
- Extranodal NK/T-cell lymphoma: an update of the molecular characterization of the tumor and microenvironment, and its clinical implications.The Lancet regional health. Western Pacific · 2025Review
- Expression and clinical significance of S100A8/9 in adults with secondary phagocytic lymphohistiocytosis.Frontiers in molecular biosciences · 2025Article
- A prognostic index for advanced-stage extranodal natural killer/T-cell lymphoma: A multicenter study.Annals of hematology · 2025Article
- Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma.Annals of hematology · 2024Article
- Article
- Clinical Efficacy of Programmed Cell Death Ligand 1 Antibody in Treatment of Extranodal Natural Killer/T-Cell Lymphoma With Hemophagocytic Lymphohistiocytosis.Journal of hematology · 2024Article
- ECSIT facilitates memory CD8Nature cell biology · 2024Article
- Review
- Article
- Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.iScience · 2023Article
- Patient-derived intrafemoral orthotopic xenografts of peripheral blood or bone marrow from acute myeloid and acute lymphoblastic leukemia patients: clinical characterization, methodology, and validation.Clinical and experimental medicine · 2023Article
- Genetic and immunohistochemical profiling of NK/T-cell lymphomas reveals prognostically relevant BCOR-MYC association.Blood advances · 2023Article
- Extranodal NK-/T-cell lymphoma, nasal type: what advances have been made in the last decade?Frontiers in oncology · 2023Review
- The mouse resource at National Resource Center for Mutant Mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2022Review
- Misaligned sequencing reads from the GNAQ-pseudogene locus may yield GNAQ artefact variants.Nature communications · 2022Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hemophagocytic syndrome (HPS) is a fatal hyperinflammatory disease with a poorly understood mechanism that occurs most frequently in extranodal natural killer/T cell lymphoma (ENKTL). Through exome sequencing of ENKTL tumor-normal samples, we have identified a hotspot mutation (c.419T>C) in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) gene, encoding a V140A variant of ECSIT. ECSIT-V140A activated NF-κB more potently than the wild-type protein owing to its increased affinity for the S100A8 and S100A9 heterodimer, which promotes NADPH oxidase activity. ECSIT-T419C knock-in mice showed higher peritoneal NADPH oxidase activity than mice with wild-type ECSIT in response to LPS. ECSIT-T419C-transfected ENKTL cell lines produced tumor necrosis factor (TNF)-α and interferon (IFN)-γ, which induced macrophage activation and massive cytokine secretion in cell culture and mouse xenografts. In individuals with ENKTL, ECSIT-V140A was associated with activation of NF-κB, higher HPS incidence, and poor prognosis. The immunosuppressive drug thalidomide prevented NF-κB from binding to the promoters of its target genes (including TNF and IFNG), and combination treatment with thalidomide and dexamethasone extended survival of mice engrafted with ECSIT-T419C-transfected ENKTL cells. We added thalidomide to the conventional dexamethasone-containing therapy regimen for two patients with HPS who expressed ECSIT-V140A, and we observed reversal of their HPS and disease-free survival for longer than 3 years. These findings provide mechanistic insights and a potential therapeutic strategy for ENKTL-associated HPS.
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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.