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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3972-3981. Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2006-09-048801. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-09-048801v1 109/9/3972    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 dos Santos, N. R Articles by Ghysdael, J. Search for Related Content PubMed PubMed Citation Articles by dos Santos, N. R Articles by Ghysdael, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 22, 2006 Accepted December 13, 2006 Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and induce T-cell leukemia Nuno R dos Santos, David S Rickman, Aurelien de Reynies, Francoise Cormier, Maryvonne Williame, Camille Blanchard, Marc-Henri Stern, and Jacques Ghysdael* Institut Curie, Centre de Recherche, Orsay, France Programme Cartes d'Identite des Tumeurs (CIT), Ligue Nationale Contre Le Cancer, Paris, France CNRS UMR146, Orsay, France Institut Curie, Centre de Recherche, Paris, France INSERM U509, Paris, France * Corresponding author; email: jacques.ghysdael{at}curie.u-psud.fr. The TEL-JAK2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. TEL-JAK2 transgenic expression in the mouse lymphoid lineage results in fatal and rapid T-cell leukemia/lymphoma. In the present report we show that T-cell leukemic cells from EµSR-TEL-JAK2 transgenic mice present an aberrant CD8-positive differentiation phenotype, as determined by the expression of stage-specific cell surface markers and lineage-specific genes. TEL-JAK2 transforms immature CD4-CD8- double-negative thymocytes, as demonstrated by the development of T-cell leukemia with full penetrance in a Rag2-deficient genetic background. This disease is similar to the bona fide TEL-JAK2 disease as assessed by phenotypic and gene profiling analyses. Pre-TCR signaling synergizes with TEL-JAK2 to transform immature thymocytes and initiate leukemogenesis as shown by (i) the delayed leukemia onset in Rag2-, CD3- and pT-deficient mice, (ii) the occurrence of recurrent chromosomal alterations in pre-TCR-deficient leukemia, and (iii) the correction of delayed leukemia onset in Rag2-deficient TEL-JAK2 mice by an H-Y TCR transgene that mimics pre-TCR signaling. Although not affecting leukemia incidence and mouse survival, TCR expression was shown to facilitate leukemic cell expansion in secondary lymphoid organs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Bessette, M. L. Lang, R. A. Fava, M. Grundy, J. Heinen, L. Horne, R. Spolski, A. Al-Shami, H. C. Morse III, W. J. Leonard, et al. A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling Blood, January 1, 2008; 111(1): 344 - 350. [Abstract] [Full Text] [PDF]

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