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Blood, 1 January 2008, Vol. 111, No. 1, pp. 309-319. Prepublished online as a Blood First Edition Paper on September 12, 2007; DOI 10.1182/blood-2007-04-085407. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2007-04-085407v1 111/1/309    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 Rawat, V. P.S. Articles by Buske, C. Search for Related Content PubMed PubMed Citation Articles by Rawat, V. P.S. Articles by Buske, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2007 Accepted September 3, 2007 Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia Vijay P.S. Rawat, Silvia Thoene, Vegi M. Naidu, Natalia Arseni, Bernhard Heilmeier, Klaus Metzeler, Konstantin Petropoulos, Aniruddha Deshpande, Leticia Quintanilla-Martinez, Stefan K. Bohlander, Karsten Spiekermann, Wolfgang Hiddemann, Michaela Feuring-Buske, and Christian Buske* Department of Medicine III, Klinikum Grosshadern, Munich, Germany Clinical Cooperative Group Leukemia, GSF - National Research Center for Environment and Health, Munich, Germany Institute of Pathology, GSF, Neuherberg, Germany * Corresponding author; email: buske{at}gsf.de. The mechanisms underlying deregulation of HOX gene expression in AML are poorly understood. The ParaHox gene CDX2 was shown to act as positive upstream regulator of several HOX genes. In this study constitutive expression of Cdx2 caused perturbation of leukemogenic Hox genes such as Hoxa10 and Hoxb8 in murine hematopoietic progenitors. Deletion of the N-terminal domain of Cdx2 abrogated its ability to perturb Hox gene expression and to cause AML in mice. In contrast inactivation of the putative Pbx interacting site of Cdx2 did not change the leukemogenic potential of the gene. In an analysis of 115 AML patients expression levels of CDX2 were closely correlated with deregulated HOX gene expression. Patients with normal karyotype showed a 14fold higher expression of CDX2 and deregulated HOX gene expression compared to patients with chromosomal translocations such as t(8:21) or t(15;17). All AML patients with normal karyotype tested were negative for CDX1 and CDX4 expression. These data link the leukemogenic potential of Cdx2 to its ability to dysregulate Hox genes. They furthermore correlate the level of CDX2 expression with HOX gene expression in human AML and support a potential role of CDX2 in the development of human AML with aberrant Hox gene expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Riedt, M. Ebinger, H. R. Salih, J. Tomiuk, R. Handgretinger, L. Kanz, F. Grunebach, and C. Lengerke Aberrant expression of the homeobox gene CDX2 in pediatric acute lymphoblastic leukemia Blood, April 23, 2009; 113(17): 4049 - 4051. [Abstract] [Full Text] [PDF] A. Saumet, G. Vetter, M. Bouttier, E. Portales-Casamar, W. W. Wasserman, T. Maurin, B. Mari, P. Barbry, L. Vallar, E. Friederich, et al. Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia Blood, January 8, 2009; 113(2): 412 - 421. [Abstract] [Full Text] [PDF] T. Haferlach Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia Hematology, January 1, 2008; 2008(1): 400 - 411. [Abstract] [Full Text] [PDF]

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