PT - JOURNAL ARTICLE AU - RICHARD JÄGER AU - JENS HAHNE AU - ANDREA JACOB AU - ANGELA EGERT AU - JOHANNES SCHENKEL AU - NICOLAS WERNERT AU - HUBERT SCHORLE AU - AXEL WELLMANN TI - Mice Transgenic for <em>NPM-ALK</em> Develop Non-Hodgkin Lymphomas DP - 2005 Sep 01 TA - Anticancer Research PG - 3191--3196 VI - 25 IP - 5 4099 - http://ar.iiarjournals.org/content/25/5/3191.short 4100 - http://ar.iiarjournals.org/content/25/5/3191.full SO - Anticancer Res2005 Sep 01; 25 AB - 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. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved