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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2375-2385. Prepublished online as a Blood First Edition Paper on December 3, 2008; DOI 10.1182/blood-2007-09-113597. This Article Full Text (PDF) Supplemental Methods and Figures Additional Supplemental Figures All Versions of this Article: blood-2007-09-113597v1 113/11/2375    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 Faber, J. Articles by Armstrong, S. A. Search for Related Content PubMed PubMed Citation Articles by Faber, J. Articles by Armstrong, S. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 26, 2007 Accepted October 23, 2008 HOXA9 is required for survival in human MLL-rearranged acute leukemias Joerg Faber, Andrei V. Krivtsov, Matthew C. Stubbs, Renee Wright, Tina N. Davis, Marry van den Heuvel-Eibrink, Christian M. Zwaan, Andrew L. Kung, and Scott A. Armstrong* Division of Hematology/Oncology, Children's Hospital, Boston, MA, United States Department of Pediatric Oncology and Harvard Medical School, Boston, MA, United States Division of Pediatric Hematology/Oncology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, Netherlands Harvard Stem Cell Institute, Boston, MA, United States * Corresponding author; email: scott.armstrong{at}childrens.harvard.edu. Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biological characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias utilizing RNAi. Gene expression profiling after HOXA9 suppression demonstrated co-downregulation of a program highly expressed in human MLL-AML and murine MLL-leukemia stem cells including HOXA10, MEIS1, PBX3 and MEF2C. We demonstrate that HOXA9 depletion in 17 human AML/ALL cell lines (7 MLL-rearranged, 10 MLL-germline) induces proliferation arrest and apoptosis specifically in MLL-rearranged cells (p=0.007). Similarly assessment of primary AMLs demonstrated HOXA9 suppression induces apoptosis to a greater extent in MLL-rearranged samples (p=0.01). Moreover, mice transplanted with HOXA9 depleted t(4;11) SEMK2 cells revealed a significantly lower leukemia burden thus identifying a role for HOXA9 in leukemia survival in vivo. Our data indicates an important role for HOXA9 in human MLL-rearranged leukemias, and suggests targeting HOXA9 or downstream programs may be a novel therapeutic option. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Might as well face it: MLL's addicted to HOX Jacquelyn J. Roth, Richard C. Crist, and Arthur M. Buchberg Blood 2009 113: 2372-2373. [Full Text] [PDF] This article has been cited by other articles: J. J. Roth, R. C. Crist, and A. M. Buchberg Might as well face it: MLL's addicted to HOX Blood, March 12, 2009; 113(11): 2372 - 2373. [Full Text] [PDF]

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