| First Author | Jäger R | Year | 2005 |
| Journal | Anticancer Res | Volume | 25 |
| Issue | 5 | Pages | 3191-6 |
| PubMed ID | 16101126 | Mgi Jnum | J:103860 |
| Mgi Id | MGI:3610807 | Citation | Jager R, et al. (2005) Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas. Anticancer Res 25(5):3191-6 |
| abstractText | 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. |
