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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2900-2907. Prepublished online as a Blood First Edition Paper on December 7, 2004; DOI 10.1182/blood-2004-09-3630. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3630v1 105/7/2900    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Landrette, S. F. Articles by Castilla, L. H. Search for Related Content PubMed PubMed Citation Articles by Landrette, S. F. Articles by Castilla, L. H. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11 Sean F. Landrette, Ya-Huei Kuo, Karen Hensen, Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Paola N. Perrat, Wim J. M. Van de Ven, Ruud Delwel, and Lucio H. Castilla From the Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA; the Laboratory for Molecular Oncology, Center for Human Genetics (CME), University of Leuven (KUL), Leuven, Belgium; and The Institute for Hematology, Erasmus Medical Center, Rotterdam, The Netherlands. Recurrent chromosomal rearrangements are associated with the development of acute myeloid leukemia (AML). The frequent inversion of chromosome 16 creates the CBFB-MYH11 fusion gene that encodes the fusion protein CBF-SMMHC. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation, and induces leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBF-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBF-SMMHC in vivo to efficiently trigger leukemia with short latency in the mouse. In addition, Plag1 and Plagl2 increased proliferation by inducing G1 to S transition that resulted in the expansion of hematopoietic progenitors and increased cell renewal in vitro. Finally, PLAG1 and PLAGL2 expression was increased in 20% of human AML samples. Interestingly, PLAGL2 was preferentially increased in samples with chromosome 16 inversion, suggesting that PLAG1 and PLAGL2 may also contribute to human AML. Overall, this study shows that Plag1 and Plagl2 are novel leukemia oncogenes that act by expanding hematopoietic progenitors expressing CbF-SMMHC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Retrovirus uncovers potent collaboration Linda Wolff Blood 2005 105: 2619. [Full Text] [PDF] This article has been cited by other articles: C. P. Pallasch, M. Patz, Y. J. Park, S. Hagist, D. Eggle, R. Claus, S. Debey-Pascher, A. Schulz, L. P. Frenzel, J. Claasen, et al. miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia Blood, October 8, 2009; 114(15): 3255 - 3264. [Abstract] [Full Text] [PDF] J. Murn, O. Alibert, N. Wu, S. Tendil, and X. Gidrol Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4 J. Exp. Med., December 22, 2008; 205(13): 3091 - 3103. [Abstract] [Full Text] [PDF] E. S. Martin, G. Tonon, R. Sinha, Y. 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