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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted July 30, 2003 Accepted October 7, 2003 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* Department of Pediatrics, Division of Hematology/Oncology/Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA; Cancer Center, University of Minnesota, Minneapolis, MN, USA * Corresponding author; email: kerse001{at}umn.edu. Identification of the targets of 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 over-expression 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? 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