Abstract
The acquisition of the Philadelphia (Ph) chromosome (or BCR-ABL translocation) represents a detrimental pathophysiological event in humans. The activated tyrosine kinases, which are produced by this translocation, are associated with fatal hematological malignancies. The initial molecular dissection of BCR-ABL has linked the expression of this constitutively activated kinase with enhanced genomic instability. We directly evaluated the consequence of BCR-ABL expression on genomic instability using the Big Blue in vivo mutagenesis mouse system. We report that the expression of BCR-ABL in both spleens and kidneys confers a mutator phenotype represented by a statistically significant elevation in mutant frequencies.
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Acknowledgements
We would like to thank Drs N Heisterkamp and J Groffen for supplying us with the P190BCR-ABL mice. This work would not have been possible without the help of colleagues in the molecular oncology group especially in Drs Allan Peaterson and Pierre Laneuville's laboratories. HFS is the recipient of a Cedar Cancer Institute and the Royal Victoria Hospital Kaufmann studentships. This work was supported by grant No. MT13253 from the Medical Research Council (MRC) of Canada to PL.
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Salloukh, H., Laneuville, P. Increase in mutant frequencies in mice expressing the BCR-ABL activated tyrosine kinase. Leukemia 14, 1401–1404 (2000). https://doi.org/10.1038/sj.leu.2401855
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DOI: https://doi.org/10.1038/sj.leu.2401855
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