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Specific inhibition of bcr-abl gene expression by small interfering RNA

Lookup NU author(s): Professor Olaf Heidenreich

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Abstract

Small interfering RNAs (siRNAs) were designed to target the bcr-abl oncogene, which causes chronic myeloid leukemia (CML) and bcr-abl-positive acute lymphoblastic leukemia (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 because 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-dependent, 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.


Publication metadata

Author(s): Scherr M, Battmer K, Winkler T, Heidenreich O, Ganser A, Eder M

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2003

Volume: 101

Issue: 4

Pages: 1566-1569

Print publication date: 26/09/2002

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

URL: http://dx.doi.org/10.1182/blood-2002-06-1685

DOI: 10.1182/blood-2002-06-1685


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