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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1685.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1566-1569
NEOPLASIA
Brief report
Specific inhibition of bcr-abl gene
expression by small interfering RNA
Michaela Scherr,
Karin Battmer,
Thomas Winkler,
Olaf Heidenreich,
Arnold Ganser, and
Matthias Eder
From the Department of Hematology and Oncology,
Hannover Medical School, Germany; and the Department of Molecular
Biology, University of Tübingen, Germany.
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.
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