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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1685.
Submitted June 11, 2002
Accepted September 14, 2002
Specific inhibition of bcr-abl gene expression by small interfering RNA
Michaela Scherr*, Karin Battmer, Thomas Winkler, Olaf Heidenreich, Arnold Ganser, and Matthias Eder
Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
Department of Molecular Biology, University of Tuebingen, Tuebingen, Germany
* Corresponding author; email: M.Scherr{at}t-online.de.
Small interfering RNAs (siRNA) were designed to target the bcr-abl oncogene which causes chronic myeloid and bcr-abl positive acute lymphoblastic leukemia (CML, ALL). Chemically synthesized anti-bcr-abl siRNAs were selected using reporter gene constructs and were found to reduce bcr-abl mRNA up to 87% in bcr-abl positive cell lines and in primary cells from CML patients. This mRNA reduction was specific for bcr-abl since both c-abl and c-bcr mRNA levels remained unaffected. Furthermore, protein expression of BCR-ABL and of laminA/C was reduced by specific siRNAs up to 80% in bcr-abl positive and normal CD34+ cells, respectively. Finally, anti-bcr-abl siRNA inhibited BCR-ABL-, but not cytokine-dependent proliferation in a bcr-abl positive cell line. These data demonstrate that siRNA can specifically and efficiently interfere with the expression of an oncogenic fusion gene in hematopoietic cells.
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