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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-05-1343. This Article Full Text (PDF) All Versions of this Article: 2002-05-1343v1 101/5/1919    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chiarle, R. Articles by Inghirami, G. G Search for Related Content PubMed PubMed Citation Articles by Chiarle, R. Articles by Inghirami, G. G Social Bookmarking                   What's this? Submitted May 30, 2002 Accepted August 21, 2002 NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors Roberto Chiarle, Jerald Z JGong, Ilaria Guasparri, Anna Pesci, Honjing Cai, Jian Liu, William J Simmons, Girish Dhall, Jennifer Howes, Roberto Piva, and Giorgio G Inghirami* Department of Pathology, New York University, New York, NY, USA Department of Pathology, University of Turin, Turin, Italy Department of Pathology, University of Verona, Verona, Italy Department of Pediatric Oncology, New York University, New York, NY, USA * Corresponding author; email: Inghig01{at}med.nyu.edu. Anaplastic Large Cell Lymphomas (ALCL) carry translocations in which the Anaplastic Lymphoma Kinase (ALK) gene is juxtaposed to various genes, the most common of which is the NPM/B23 gene. ALK fusion proteins result in the constitutive activation of ALK tyrosine kinase, thereby enhancing proliferation and increasing cell survival. A direct role for NPM-ALK in cellular transformation has been shown in vitro with immortalized cell lines and in vivo using retroviral transfer experiments. Nonetheless, there is no direct evidence of its oncogenic potential in T lymphocytes, which represent the most common target of ALK chimeras. Here, we describe a new mouse model of lymphomagenesis in which human NPM-ALK transcription was targeted to T cells. NPM-ALK transgenic (Tg) mice were born with the expected mendelian distribution, normal lymphoid organs and a normal number and proportion of helper and suppressor T cells. However, after a short period of latency, all NPM-ALK transgenic (Tg) mice developed malignant lymphoproliferative disorders (mean survival 18 weeks). NPM-ALK Tg thymic lymphomas displayed a T cell phenotype characteristic of immature thymocytes and frequently coexpressed surface CD30. A subset of the NPM-ALK Tg mice also developed clonal B cell plasma cell neoplasms. These tumors arose in peripheral lymphoid organs (plasmacytomas) or within the bone marrow and often led to peripheral neuropathies and limb paralysis. Our NPM-ALK transgenic mice are a suitable model to dissect the molecular mechanisms of ALK-mediated transformation and to investigate the efficacy of new therapeutic approaches for the treatment of human ALCL in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Ambrogio, C. Martinengo, C. Voena, F. Tondat, L. Riera, P. F. di Celle, G. Inghirami, and R. Chiarle NPM-ALK Oncogenic Tyrosine Kinase Controls T-Cell Identity by Transcriptional Regulation and Epigenetic Silencing in Lymphoma Cells Cancer Res., November 15, 2009; 69(22): 8611 - 8619. [Abstract] [Full Text] [PDF] Y. P. Mosse, A. Wood, and J. M. Maris Inhibition of ALK Signaling for Cancer Therapy Clin. Cancer Res., September 15, 2009; 15(18): 5609 - 5614. [Abstract] [Full Text] [PDF] M. 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