ArticleLeukemia2014
JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 153 citations in OpenAlex.
- Trial
- Role of PRDM1 in natural killer cells.Molecular biology reports · 2026Review
- From molecular pathogenesis to novel Therapeutic approaches - a review of recent advances in the treatment of peripheral T cell Lymphomas.Biomarker research · 2026Review
- Primary gastric EBV-positive cytotoxic-molecule-negative T-cell lymphoma with TET2 multihit mutations: a case report.Journal of clinical and experimental hematopathology : JCEH · 2026Article
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic lymphohistiocytosis-a Rare and Dangerous Disease.Blood and lymphatic cancer : targets and therapy · 2026Review
- Impact of rare JAK/STAT germline mutations on vaccination-induced innate immune responses in a Tyrolian population.International journal of biological sciences · 2026Article
- Investigation of the transcriptional impact of rare germline JAK/STAT variants found in a Tyrolean alpine community.BMC genomics · 2025Article
- 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
- Thyroid hormones contribute to JAK/STAT pathway abnormal activation, promoting T-cell lymphoma dissemination.Blood advances · 2025Article
- Butyrate-producingGut · 2025Article
- Spotlight on amino acid changing mutations in the JAK-STAT pathway: from disease-specific mutation to general mutation databases.Scientific reports · 2025Article
- Functional screening of somatic mutant events in extranodal natural killer/T-cell lymphoma with adrenal involvement.Frontiers in immunology · 2025Article
- Janus Kinase 3 (JAK3): A Critical Conserved Node in Immunity Disrupted in Immune Cell Cancer and Immunodeficiency.International journal of molecular sciences · 2024Review
- Idiopathic erythrocytosis: a germline disease?Clinical and experimental medicine · 2024Article
- Biology and genetics of extranodal mature T-cell and NKcell lymphomas and lymphoproliferative disorders.Haematologica · 2023Review
- Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.iScience · 2023Article
- JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation.International journal of molecular sciences · 2023Article
- Novel target and treatment agents for natural killer/T-cell lymphoma.Journal of hematology & oncology · 2023Review
- Mature T-cell and NK-cell lymphomas: updates on molecular genetic features.International journal of hematology · 2023Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extranodal, nasal-type natural killer (NK)/T-cell lymphoma (NKCL) is an aggressive malignancy with poor prognosis in which, usually, signal transducer and activator of transcription 3 (STAT3) is constitutively activated and oncogenic. Here, we demonstrate that STAT3 activation mostly results from constitutive Janus kinase (JAK)3 phosphorylation on tyrosine 980, as observed in three of the four tested NKCL cell lines and in 20 of the 23 NKCL tumor samples under study. In one of the cell lines and in 4 of 19 (21%) NKCL primary tumor samples, constitutive JAK3 activation was related to an acquired mutation (A573V or V722I) in the JAK3 pseudokinase domain. We then show that constitutive activation of the JAK3/STAT3 pathway has a major role in NKCL cell growth and survival and in the invasive phenotype. Indeed, NKCL cell growth was slowed down in vitro by targeting JAK3 with chemical inhibitors or small-interfering RNAs. In a human NKCL xenograft mouse model, tumor growth was significantly delayed by the JAK3 inhibitor CP-690550. Altogether, the constitutive activation of JAK3, which can result from JAK3-activating mutations, is a frequent feature of NKCL that deserves to be tested as a therapeutic target.
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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.