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Prepublished online as a Blood First Edition Paper on August 28, 2003; DOI 10.1182/blood-2003-06-2163. This Article Full Text (PDF) All Versions of this Article: 2003-06-2163v1 103/1/229    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 Poppe, B. Articles by Speleman, F. Search for Related Content PubMed PubMed Citation Articles by Poppe, B. Articles by Speleman, F. Social Bookmarking                   What's this? Submitted June 30, 2003 Accepted August 22, 2003 Expression analyses identify MLL as a prominent target of 11q23 amplification and support an etiologic role for MLL gain of function in myeloid malignancies Bruce Poppe, Jo Vandesompele, Claudia Schoch, Charlotta Lindvall, Krzysztof Mrozek, Clara D Bloomfield, H Berna Beverloo, Lucienne Michaux, Nicole Dastugue, Christian Herens, Nurten Yigit, Anne De Paepe, Anne Hagemeijer, and Frank Speleman* Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium Laboratory for Leukemia Diagnostics, University Hospital Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany Department of Molecular Medicine, Karolinska Hospital and Institute, Stockholm, Sweden Division of Hematology and Oncology, Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH, USA Departments of Clinical Genetics/Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands Department of Hematology and Center for Human Genetics, Cliniques Universitaires Saint-Luc, Brussels, Belgium Department of Human Genetics, CHU Sart Tilman, Liege, Belgium Laboratoire d'Hematologie, CHU Toulouse, Toulouse, France Centre for Human Genetics, University of Leuven, Leuven, Belgium * Corresponding author; email: franki.speleman{at}UGent.be. MLL amplification was recently recognized as a recurrent aberration in AML and MDS, associated with adverse prognosis and karyotype complexity. Here we present detailed results of FISH and expression analyses of MLL and 5 selected 11q candidate oncogenes (CBL, DDX6, ETS1, FLI1 and PLZF) in 31 patient samples and one cell line with 11q23 gain. FISH analyses revealed that the 11q23 amplicon invariably encompassed MLL, DDX6, ETS1 and FLI1, while expression analyses identified MLL and DDX6 as the most differentially expressed genes among samples with and without 11q23 copy gain or amplification. In MLL amplified samples, a significant transcriptional upregulation of MEIS1, PROML1, ADAM10, NKG2D and ITPA was noted. Further analyses, designed to elucidate a possible role of the 11q overexpressed genes (MLL, DDX6, FLI1 and ETS1) in unselected MDS and AML samples, revealed a significant upregulation of MLL in MDS. Our findings confirm the MLL gene as a prominent target of 11q23 amplification and provide further evidence for an etiologic role for MLL gain of function in myeloid malignancies. In addition, our results indicate that the transcriptional program associated with MLL rearrangements and MLL overexpression displays significant similarities. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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