Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas
Jäger, R.; Hahne, J.; Jacob, A.; Egert, A.; Schenkel, J.; Wernert, N.; Schorle, H.; Wellmann, A.
Anticancer Research 25(5): 3191-3196
2005
ISSN/ISBN: 0250-7005 PMID: 16101126 Document Number: 593979
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.