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

Leukemia volume 19, pages 1859–1862 (2005)Cite this article

Abstract

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.

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Acknowledgements

LCC is the recipient of a Clinical Research Fellowship from the Leukaemia Research Fund of Great Britain. MWD is a Junior Faculty Scholar of the American Society of Hematology. The Howard Hughes Medical Institute (BJD), the Doris Duke Charitable Foundation (BJD), The Leukemia and Lymphoma Society (BJD), the TJ Martell Foundation (BJD) and the Burroughs Wellcome Fund (BJD) supported this work. We thank Kara Johnson for helpful advice and Chris Koontz for administrative assistance. We thank Bristol-Myers Squibb for the generous donation of dasatinib.

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Authors and Affiliations

  1. Oregon Health & Science University Cancer Institute, Portland, OR, USA

    L C Crossman, T O'Hare, S G Willis, E P Stoffregen, A S Corbin, M C Heinrich, B J Druker & M W N Deininger

  2. Academic Haematology, University of Newcastle upon Tyne, UK

    L C Crossman, S G O'Brien & P G Middleton

  3. Department of Haematology/Oncology, University of Leipzig, Germany

    T Lange

  4. Howard Hughes Medical Institute, USA

    M C Heinrich & B J Druker

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  1. L C Crossman
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  2. T O'Hare
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Correspondence to L C Crossman.

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Crossman, L., O'Hare, T., Lange, T. et al. A single nucleotide polymorphism in the coding region of ABL and its effects on sensitivity to imatinib. Leukemia 19, 1859–1862 (2005). https://doi.org/10.1038/sj.leu.2403935

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