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Blood, 1 January 2007, Vol. 109, No. 1, pp. 281-289. Prepublished online as a Blood First Edition Paper on September 12, 2006; DOI 10.1182/blood-2006-03-009670. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2006-03-009670v1 109/1/281    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 Souabni, A. Articles by Busslinger, M. Search for Related Content PubMed PubMed Citation Articles by Souabni, A. Articles by Busslinger, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 13, 2006 Accepted August 16, 2006 Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus Abdallah Souabni, Wolfram Jochum, and Meinrad Busslinger* Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna Austria Department of Pathology, University Hospital, Zurich, Switzerland * Corresponding author; email: busslinger{at}imp.univie.ac.at. Four of 9 PAX transcription factor genes have been associated with chromosomal translocations in human tumors, although their oncogenic potential has not yet been demonstrated in transgenic mouse models. The B-lymphoid PAX5 gene participates in the generation of the t(9;14)(p13;q32) translocation in germinal center B-cells, which leads to deregulated PAX5 expression under the control of the immunoglobulin heavy-chain (IgH) locus in a subset of B-cell non-Hodgkin’ s lymphomas. Here we reconstructed a human t(9;14) translocation in a knock-in mouse by inserting a PAX5 minigene into the IgH locus. The IgHP5ki allele, which corresponds to a germline rather than somatic mutation, is activated in multipotent hematopoietic progenitors and is subsequently expressed in DC, NK, T and B cells. Ectopic Pax5 expression interferes with normal T-cell development and causes immature T-lymphoblastic lymphomas in IgHP5ki/+ and IgHP5ki/P5ki mice. Aggressive T-cell lymphomas develop even faster in IkPax5/+ mice expressing Pax5 from the Ikaros locus. Pax5 expression in thymocytes activates B-cell-specific genes and represses T-lymphoid genes, suggesting that Pax5 contributes to lymphomagenesis by deregulating the T-cell gene expression program. These data identify Pax5 as a potent oncogene and demonstrate that the T-lymphoid lineage is particularly sensitive to the oncogenic action of Pax5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Nowak, D. Stewart, and H. P. Koeffler Differentiation therapy of leukemia: 3 decades of development Blood, April 16, 2009; 113(16): 3655 - 3665. [Abstract] [Full Text] [PDF] M. Yan, N. Himoudi, M. Pule, N. Sebire, E. Poon, A. Blair, O. Williams, and J. Anderson Development of Cellular Immune Responses against PAX5, a Novel Target for Cancer Immunotherapy Cancer Res., October 1, 2008; 68(19): 8058 - 8065. [Abstract] [Full Text] [PDF] N. Kawamata, S. Ogawa, M. Zimmermann, B. Niebuhr, C. Stocking, M. Sanada, K. Hemminki, G. Yamatomo, Y. Nannya, R. Koehler, et al. Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray PNAS, August 19, 2008; 105(33): 11921 - 11926. [Abstract] [Full Text] [PDF] F. Mora-Lopez, E. Reales, J. A. Brieva, and A. Campos-Caro Human BSAP and BLIMP1 conform an autoregulatory feedback loop Blood, November 1, 2007; 110(9): 3150 - 3157. [Abstract] [Full Text] [PDF]

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