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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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 2005
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| In: |
Anticancer research
Year: 2005, Volume: 25, Issue: 5, Pages: 3191-3196 |
| ISSN: | 1791-7530 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/25/5/3191
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| Author Notes: | Richard Jäger, Jens Hahne, Andrea Jacob, Angela Egert, Johannes Schenkel, Nicolas Wernert, Hubert Schorle and Axel Wellmann |
| Summary: | 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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| Item Description: | Gesehen am 05.05.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1791-7530 |