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A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib

Lookup NU author(s): Dr Lucy Crossman, Professor Stephen O'Brien, Dr Peter Middleton


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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.

Publication metadata

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


DOI: 10.1038/sj.leu.2403935

PubMed id: 16151465


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