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.
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 humanNPM-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.
Authors: Leah C Young; Kathleen M Bone; Peng Wang; Fang Wu; Benjamin A Adam; Samar Hegazy; Pascal Gelebart; Jelena Holovati; Liang Li; Susan E Andrew; Raymond Lai Journal: Am J Pathol Date: 2011-05-24 Impact factor: 4.307
Authors: Fiona K E Mduff; C Elizabeth Hook; Reuben M Tooze; Brian J Huntly; Pier Paolo Pandolfi; Suzanne D Turner Journal: Lab Invest Date: 2011-06-27 Impact factor: 5.662
Authors: Tim I M Malcolm; Patrick Villarese; Camilla J Fairbairn; Laurence Lamant; Amélie Trinquand; C Elizabeth Hook; G A Amos Burke; Laurence Brugières; Katherine Hughes; Dominique Payet; Olaf Merkel; Ana-Iris Schiefer; Ibraheem Ashankyty; Shahid Mian; Mariusz Wasik; Martin Turner; Lukas Kenner; Vahid Asnafi; Elizabeth Macintyre; Suzanne D Turner Journal: Nat Commun Date: 2016-01-12 Impact factor: 14.919