Browse by author
Lookup NU author(s): Dr Lucy Crossman, Professor Stephen O'Brien, Dr Peter Middleton
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
We have identified a gene polymorphism (K247R) within or close to the P-loop of BCR-ABL, which leads to the substitution of arginine for lysine. We investigated the allelic frequency of K247R by screening 157 CML patients and 213 healthy blood donors with conventional sequencing, restriction enzyme digest and single strand conformational polymorphism analysis, and found the arginine allele to be rare. Three out of five CML patients with the arginine allele of K247R failed to achieve a major cytogenetic response to imatinib, suggesting that the arginine allele may have reduced sensitivity. However, despite K247R's position in or near to the P-loop, biochemical and cellular assays of imatinib and dasatinib sensitivity showed no alteration compared to wild type. Clinicians should be aware that possession of the arginine allele of K247R does not reflect a mutation that necessitates a change in the therapeutic strategy, unless there are other signs of inadequate response to drug. © 2005 Nature Publishing Group. All rights reserved.
Author(s): Crossman LC, O'Hare T, Lange T, Willis S, Stoffregen EP, Corbin AS, O'Brien SG, Heinrich MC, Druker BJ, Middleton PG, Deininger MWN
Publication type: Article
Publication status: Published
Journal: Leukemia
Year: 2005
Volume: 19
Issue: 11
Pages: 1859-1862
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
URL: http://dx.doi.org/10.1038/sj.leu.2403935
DOI: 10.1038/sj.leu.2403935
PubMed id: 16151465
Altmetrics provided by Altmetric
