ArticleLeukemia2016
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- [Current status and progress in the diagnosis and treatment of monomorphic epitheliotropic intestinal T-cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Pooled it
- Multivariable genome-wide analysis elucidates the shared genetic architecture, immunosenescence features, and gut-origin therapeutic targets of ulcerative colitis-associated multisystem inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Indolent natural killer-cell lymphoproliferative disorder of the gallbladder: a rare case report.Frontiers in oncology · 2026Article
- Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma.Leukemia · 2026Article
- Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of LSD1 and OXPHOS.Cell reports · 2025Article
- Comprehensive investigation of gene mutations in canine large cell gastrointestinal lymphoma.Frontiers in veterinary science · 2025Article
- Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- Investigation of the mutations in the genes involved in Janus kinase/signal transducer and activator of transcription pathway in canine large cell gastrointestinal lymphoma.The Journal of veterinary medical science · 2024Article
- Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine.European journal of medical research · 2024Article
- Single nucleotide polymorphism profiles of canine T-cell and null-cell lymphomas.Frontiers in veterinary science · 2024Article
- Development of a high-density sub-species-specific targeted SNP assay for Rocky Mountain bighorn sheep (PeerJ · 2024Article
- Few and far between: clinical management of rare extranodal subtypes of mature T-cell and NK-cell lymphomas.Haematologica · 2023Review
- Biology and genetics of extranodal mature T-cell and NKcell lymphomas and lymphoproliferative disorders.Haematologica · 2023Review
- Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer.Frontiers in immunology · 2023Article
- Refractory celiac disease and its mimickers: a review on pathogenesis, clinical-pathological features and therapeutic challenges.Frontiers in oncology · 2023Review
- The implication of next-generation sequencing in the diagnosis and clinical management of non-Hodgkin lymphomas.Frontiers in oncology · 2023Review
- The complementary roles of STAT3 and STAT1 in cancer biology: insights into tumor pathogenesis and therapeutic strategies.Frontiers in immunology · 2023Review
- How molecular advances may improve the diagnosis and management of PTCL patients.Frontiers in oncology · 2023Review
- Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis.Molecular pharmacology · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
45 authors at 16 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
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