ArticleThe Journal of experimental medicine2010
The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- Results from an open-label phase 2a study of cerdulatinib, a dual spleen tyrosine kinase/janus kinase inhibitor, in relapsed/refractory peripheral T-cell lymphoma.Leukemia & lymphoma · 2025Trial
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Targeting SYK to alleviate MDSC-driven immunosuppression and augment anti-PD1 efficacy.Science China. Life sciences · 2026Article
- Genome-epigenome crosstalk in T-cell lymphomas: from maps to mechanisms.International journal of hematology · 2026Review
- Benchmarking spleen tyrosine kinase (Syk) expression in T- and NK-cell neoplasms: Implications for therapeutic targeting.British journal of haematology · 2025Article
- Differential regulatory effects of the N-terminal region in SYK-fusion kinases reveal unique activation-inducible nuclear translocation of ITK-SYK.Scientific reports · 2025Article
- Review
- Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2024Article
- Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China.Frontiers in immunology · 2024Article
- TCR Pathway Mutations in Mature T Cell Lymphomas.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma.Nature cancer · 2023Article
- SOHO State of the Art Updates and Next Questions | New Pathways and New Targets in PTCL: Staying on Target.Clinical lymphoma, myeloma & leukemia · 2023Review
- ITK degradation to block T cell receptor signaling and overcome therapeutic resistance in T cell lymphomas.Cell chemical biology · 2023Article
- Tyrosine kinases in nodal peripheral T-cell lymphomas.Frontiers in oncology · 2023Review
- Epigenetic targets in B- and T-cell lymphomas: latest developments.Therapeutic advances in hematology · 2023Review
- Article
- Recent Advances in the Management of Relapsed and Refractory Peripheral T-Cell Lymphomas.Journal of personalized medicine · 2022Review
- A preclinical model of peripheral T-cell lymphoma GATA3 reveals DNA damage response pathway vulnerability.EMBO molecular medicine · 2022Article
- Novel T Follicular Helper-like T-Cell Lymphoma Therapies: From Preclinical Evaluation to Clinical Reality.Cancers · 2022Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peripheral T cell lymphomas (PTCLs) are highly aggressive malignancies with poor prognosis. Their molecular pathogenesis is not well understood and small animal models for the disease are lacking. Recently, the chromosomal translocation t(5;9)(q33;q22) generating the interleukin-2 (IL-2)-inducible T cell kinase (ITK)-spleen tyrosine kinase (SYK) fusion tyrosine kinase was identified as a recurrent event in PTCL. We show that ITK-SYK associates constitutively with lipid rafts in T cells and triggers antigen-independent phosphorylation of T cell receptor (TCR)-proximal proteins. These events lead to activation of downstream pathways and acute cellular outcomes that correspond to regular TCR ligation, including up-regulation of CD69 or production of IL-2 in vitro or deletion of thymocytes and activation of peripheral T cells in vivo. Ultimately, conditional expression of patient-derived ITK-SYK in mice induces highly malignant PTCLs with 100% penetrance that resemble the human disease. Our work demonstrates that constitutively enforced antigen receptor signaling can, in principle, act as a powerful oncogenic driver. Moreover, we establish a robust clinically relevant and genetically tractable model of human PTCL.
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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.