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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1823-1828. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-07-2582. This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 2003-07-2582v1 103/5/1823    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 Kumar, A. R. Articles by Kersey, J. H. Search for Related Content PubMed PubMed Citation Articles by Kumar, A. R. Articles by Kersey, J. 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 Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia Ashish R. Kumar, Wendy A. Hudson, Weili Chen, Ritsuo Nishiuchi, Qing Yao, and John H. Kersey From the Department of Pediatrics, Division of Hematology/Oncology/Blood and Marrow Transplantation, and the Cancer Center, University of Minnesota, Minneapolis. Identification of the targets of mixed lineage leukemia (MLL) fusion genes will assist in understanding the biology of MLL fusion gene leukemias and in development of better therapies. Numerous studies have implicated HOXA9 as one of the possible targets of MLL fusion proteins. To determine if HOXA9 was required for leukemia development by MLL fusion genes, we compared the effects of the Mll-AF9 knock-in mutation in mice in the presence or absence of Hoxa9. Both groups of mice showed myeloid expansion at 8 weeks and then developed myeloid leukemia with a similar incidence and time course. The leukemia in the mice lacking Hoxa9 generally displayed a more immature myeloid phenotype than that in the mice that were wild-type for Hoxa9. Gene expression profiling revealed that expression of Mll-AF9 led to overexpression of Hoxa5, Hoxa6, Hoxa7, Hoxa9, and Hoxa10. Thus, genes of the Hox-a cluster are important in defining the phenotype but not the incidence of Mll-AF9 leukemia. These results demonstrate that the Mll-AF9 fusion gene disrupts the expression of several Hox genes, none of which as a single gene is likely to be necessary for development of leukemia. Instead, we propose that the "Hox code" minimally defined by the Hoxa5-a9 cluster is central to MLL leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: More complexity in MLL-associated leukemias Keith Humphries Blood 2004 103: 1566-1567. [Full Text] [PDF] This article has been cited by other articles: M. Schwieger, A. Schuler, M. Forster, A. Engelmann, M. A. Arnold, R. Delwel, P. J. Valk, J. Lohler, R. K. Slany, E. N. Olson, et al. Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C Blood, September 17, 2009; 114(12): 2476 - 2488. [Abstract] [Full Text] [PDF] M. Liedtke and M. L. Cleary Therapeutic targeting of MLL Blood, June 11, 2009; 113(24): 6061 - 6068. [Abstract] [Full Text] [PDF] J. Faber, A. V. Krivtsov, M. C. Stubbs, R. Wright, T. N. Davis, M. van den Heuvel-Eibrink, C. M. Zwaan, A. L. Kung, and S. A. 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Iwasaki, T. C.P. Somervaille, C. W. E. So, and M. L. Cleary Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential Genes & Dev., November 1, 2007; 21(21): 2762 - 2774. [Abstract] [Full Text] [PDF] S. Lindsey, W. Huang, H. Wang, E. Horvath, C. Zhu, and E. A. Eklund Activation of SHP2 Protein-tyrosine Phosphatase Increases HoxA10-induced Repression of the Genes Encoding gp91PHOX and p67PHOX J. Biol. Chem., January 26, 2007; 282(4): 2237 - 2249. [Abstract] [Full Text] [PDF] K. Y. Chung, G. Morrone, J. J. Schuringa, M. Plasilova, J.-H. Shieh, Y. Zhang, P. Zhou, and M. A.S. Moore Enforced Expression of NUP98-HOXA9 in Human CD34+ Cells Enhances Stem Cell Proliferation Cancer Res., December 15, 2006; 66(24): 11781 - 11791. [Abstract] [Full Text] [PDF] D. Bansal, C. Scholl, S. Frohling, E. McDowell, B. H. Lee, K. Dohner, P. Ernst, A. J. Davidson, G. Q. Daley, L. I. Zon, et al. Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model PNAS, November 7, 2006; 103(45): 16924 - 16929. [Abstract] [Full Text] [PDF] W. Chen, Q. Li, W. A. Hudson, A. Kumar, N. Kirchhof, and J. H. Kersey A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy Blood, July 15, 2006; 108(2): 669 - 677. [Abstract] [Full Text] [PDF] S. J. Horton, D. G. Grier, G. J. McGonigle, A. Thompson, M. Morrow, I. De Silva, D. A. Moulding, D. Kioussis, T. R.J. Lappin, H. J.M. Brady, et al. Continuous MLL-ENL Expression Is Necessary to Establish a "Hox Code" and Maintain Immortalization of Hematopoietic Progenitor Cells Cancer Res., October 15, 2005; 65(20): 9245 - 9252. [Abstract] [Full Text] [PDF] L. Bei, Y. Lu, and E. A. Eklund HOXA9 Activates Transcription of the Gene Encoding gp91Phox during Myeloid Differentiation J. Biol. Chem., April 1, 2005; 280(13): 12359 - 12370. 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