Mice transgenic for NPM-ALK develop non-hodgkin lymphomas

Background: The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype. The translocation produces an 80 kDa hyperphosphorylated chimeric protein (p80) derived from the fusion of the anaplastic lymphoma kinase (ALK) w...

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Hauptverfasser: Jäger, Richard (VerfasserIn) , Hahne, Jens Claus (VerfasserIn) , Jacob, Andrea (VerfasserIn) , Egert, Angela (VerfasserIn) , Schenkel, Johannes (VerfasserIn) , Wernert, Nicolas (VerfasserIn) , Schorle, Hubert (VerfasserIn) , Wellmann, Axel (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: September 2005
In: Anticancer research
Year: 2005, Jahrgang: 25, Heft: 5, Pages: 3191-3196
ISSN:1791-7530
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/25/5/3191
Volltext
Verfasserangaben:Richard Jäger, Jens Hahne, Andrea Jacob, Angela Egert, Johannes Schenkel, Nicolas Wernert, Hubert Schorle and Axel Wellmann

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520 |a Background: The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype. The translocation produces an 80 kDa hyperphosphorylated chimeric protein (p80) derived from the fusion of the anaplastic lymphoma kinase (ALK) with nucleophosmin (NPM). The NPM-ALK chimeric protein is an activated tyrosine kinase that has been shown to be a potent oncogene and presumably plays a causative role in lymphomagenesis. Materials and Methods: A transgenic mouse line was generated, where the human NPM-ALK cDNA is driven by the lck promoter conferring transgene expression to early T-cells. Results: Mice rapidly developed large cell lymphoblastic lymphomas with a median latency of 8 weeks, primarily involving the thymus, with lymph node as well as histologically evident extranodal organ infiltration by large tumor cells. Conclusion: The transgenic approach described provides direct evidence for the strong transforming potential of NPM-ALK in T-cells and furthermore represents a system for the analysis of the oncogenic events mediated by NPM-ALK in vivo, which might be instrumental in the development of tyrosine kinase inhibitor therapies of potential clinical use. 
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