title: Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Pathology, Department of Developmental Pathology, University of Bonn Medical School, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Jäger
authors.forename: Jens
authors.initials: J
authors.lastname: Hahne
authors.forename: Andrea
authors.initials: A
authors.lastname: Jacob
authors.forename: Angela
authors.initials: A
authors.lastname: Egert
authors.forename: Johannes
authors.initials: J
authors.lastname: Schenkel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
authors.forename: Hubert
authors.initials: H
authors.lastname: Schorle
authors.forename: Axel
authors.initials: A
authors.lastname: Wellmann
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000201:enzymology / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology
chemical_list: C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)