TY - JOUR A1 - Jäger, Richard A1 - Hahne, Jens A1 - Jacob, Andrea A1 - Egert, Angela A1 - Schenkel, Johannes A1 - Wernert, Nicolas A1 - Schorle, Hubert A1 - Wellmann, Axel T1 - Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas T2 - Anticancer Res. (Anticancer Research) N2 - 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. Y1 - 2005 UR - https://pub.h-brs.de/frontdoor/index/index/docId/3748 UR - http://ar.iiarjournals.org/content/25/5/3191 SN - 0250-7005 VL - 25 IS - 5 SP - 3191 EP - 3196 PB - International Institute of Anticancer Research ER -