We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.

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.

Pubmed ID: 20439541 RIS Download

Mesh terms: Animals | Antigens, CD | Antigens, Differentiation, T-Lymphocyte | Chromosomes, Human, Pair 5 | Chromosomes, Human, Pair 9 | Disease Models, Animal | Embryonic Stem Cells | Gene Expression Regulation, Neoplastic | Humans | Interleukin-2 | Intracellular Signaling Peptides and Proteins | Lectins, C-Type | Lymphoma, T-Cell, Peripheral | Lymphoproliferative Disorders | Mice | Protein-Tyrosine Kinases | Receptors, Antigen, T-Cell | Recombinant Fusion Proteins | Signal Transduction | Spleen | Syk Kinase | Translocation, Genetic

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants


Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.