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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-12-3899. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-12-3899v1 102/6/2236    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 Wohlbold, L. Articles by Aulitzky, W. E. Search for Related Content PubMed PubMed Citation Articles by Wohlbold, L. Articles by Aulitzky, W. E. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2003, Vol. 102, No. 6, pp. 2236-2239 NEOPLASIA Brief report Inhibition of bcr-abl gene expression by small interfering RNA sensitizes for imatinib mesylate (STI571) Lara Wohlbold, Heiko van der Kuip, Cornelius Miething, Hans-Peter Vornlocher, Cornelius Knabbe, Justus Duyster, and Walter E. Aulitzky From the Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; 2nd Department of Internal Medicine, Oncology and Hematology, Robert Bosch Hospital, Stuttgart, Germany; Department of Internal Medicine III, Technical University of Munich, Germany; Ribopharma AG, Kulmbach, Germany; Department of Clinical Chemistry, Robert Bosch Hospital, Stuttgart, Germany. Bcr-Abl proteins are effective inducers of the leukemic phenotype in chronic myeloid leukemia (CML) and distinct variants of acute lymphoblastic leukemia (ALL). Targeting bcr-abl by treatment with the selective tyrosine kinase inhibitor imatinib has proved to be highly efficient for controlling leukemic growth. However, it is unclear whether imatinib is sufficient to eradicate the disease because of primary or secondary resistance of leukemic cells. Therefore, targeting Bcr-Abl with an alternative approach is of great interest. We demonstrate that RNA interference (RNAi) with a breakpoint-specific short-interfering RNA (siRNA) is capable of decreasing Bcr-Abl protein expression and of antagonizing Bcr-Abl–induced biochemical activities. RNAi selectively inhibited Bcr-Abl–dependent cell growth. Furthermore, bcr-abl–homologous siRNA increased sensitivity to imatinib in Bcr-Abl–overexpressing cells and in a cell line expressing the imatinib-resistant Bcr-Abl kinase domain mutation His396Pro, thereby antagonizing 2 of the major mechanisms of resistance to imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Koldehoff, D. W. Beelen, and A. H. Elmaagacli Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma J. Leukoc. Biol., August 1, 2008; 84(2): 561 - 576. [Abstract] [Full Text] [PDF] V. Rapozzi, S. Cogoi, and L. E. Xodo Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells. Mol. Cancer Ther., July 1, 2006; 5(7): 1683 - 1692. [Abstract] [Full Text] [PDF] M. Scherr, A. Chaturvedi, K. Battmer, I. Dallmann, B. Schultheis, A. Ganser, and M. Eder Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML) Blood, April 15, 2006; 107(8): 3279 - 3287. [Abstract] [Full Text] [PDF] J. Cortes and H. Kantarjian New Targeted Approaches in Chronic Myeloid Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6316 - 6324. [Abstract] [Full Text] [PDF] C. A. Sledz and B. R. G. Williams RNA interference in biology and disease Blood, August 1, 2005; 106(3): 787 - 794. [Abstract] [Full Text] [PDF] M. Stevenson Therapeutic Potential of RNA Interference N. Engl. J. Med., October 21, 2004; 351(17): 1772 - 1777. [Full Text] [PDF]

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