| First Author | Turner SD | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 49 | Pages | 7750-61 |
| PubMed ID | 14586401 | Mgi Jnum | J:86490 |
| Mgi Id | MGI:2680237 | Doi | 10.1038/sj.onc.1207048 |
| Citation | Turner SD, et al. (2003) Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase. Oncogene 22(49):7750-61 |
| abstractText | Anaplastic large-cell lymphoma is associated with a chromosomal translocation generating an oncogenic fusion protein: the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). We have generated several independent lines of human NPM-ALK transgenic mice using the haematopoietic cell-specific Vav promoter. Lymphomas develop in two transgenic lines in which the Vav promoter regulates NPM-ALK expression. The transgenic line with higher copy number displays an early-onset phenotype in which all mice succumb to aggressive lymph node tumours with intestinal involvement, whereas the second line displays late-onset tumour development in the spleen and/or liver. Lymphomas from both lines are phenotypically distinct and display B-lineage characteristics with aberrant coexpression of myeloid markers. The NPM-ALK kinase is active in primary tumour tissue and forms a multimeric complex with tyrosine-phosphorylated proteins, that is, Shc. Jun and ERK kinase activities in tumours are elevated by up to 30-fold and fivefold, respectively, in comparison with sIgM-stimulated primary B cells. The new transgenic models provide a system for investigating the oncogenic events mediated by NPM-ALK in situ and a physiologically relevant context for developing tyrosine kinase inhibitor therapies of potential use in the clinic.Oncogene (2003) 22, 7750-7761. doi:10.1038/sj.onc.1207048 |
