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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-05-1589. This Article Full Text (PDF) All Versions of this Article: 2002-05-1589v1 101/8/3157    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 Heidenreich, O. Articles by Nordheim, A. Search for Related Content PubMed PubMed Citation Articles by Heidenreich, O. Articles by Nordheim, A. Social Bookmarking                   What's this? Submitted June 5, 2002 Accepted November 23, 2002 AML1/MTG8 Oncogene Suppression by Small Interfering RNAs Supports Myeloid Differentiation of t(8;21)-positive Leukemic Cells Olaf Heidenreich*, Juergen Krauter, Heidemarie Riehle, Philipp Hadwiger, Matthias John, Gerhard Heil, Hans-Peter Vornlocher, and Alfred Nordheim Molecular Biology, University of Tuebingen, Tuebingen, Germany Hematology and Oncology, Medical School Hannover, Hannover, Germany Ribopharma AG, Kulmbach, Germany * Corresponding author; email: olaf.heidenreich{at}uni-tuebingen.de. The translocation t(8;21) yields the leukemic fusion gene AML1/MTG8 and is associated with 10-15% of all de novo cases of acute myeloid leukemia. We demonstrate the efficient and specific suppression of AML1/MTG8 by small interfering RNAs (siRNAs) in the human leukemic cell lines Kasumi-1 and SKNO-1. siRNAs targeted against the fusion site of the AML1/MTG8 mRNA reduce the levels of AML1/MTG8 without affecting the amount of wildtype AML1. These data argue against a transitive RNA interference mechanism potentially induced by siRNAs in such leukemic cells. Depletion of AML1/MTG8 correlates with an increased susceptibility of both Kasumi-1 and SKNO-1 cells to TGF1/vitamin D3-induced differentiation, leading to increased expression of CD11b, M-CSF receptor and C/EBP. Moreover, siRNA-mediated AML1/MTG8 suppression results in changes in cell shape, and, in combination with TGF1/vitamin D3, severely reduces clonogenicity of Kasumi-1 cells. These results suggest an important role for AML1/MTG8 in preventing differentiation, thereby propagating leukemic blast cells. Therefore, siRNAs are promising tools for a functional analysis of AML1/MTG8, and may be used in a molecularly defined therapeutic approach for t(8;21)-positive leukemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Osman, V. Gobert, F. Ponthan, O. Heidenreich, M. 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