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Reply: The BIM deletion polymorphism cannot account for intrinsic TKI resistance of Chinese individuals with chronic myeloid leukemia

Nature Medicine volume 20, pages 1090–1091 (2014)Cite this article

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Ong et al. reply:

We acknowledge the interest of Chen et al.1 in our recent publication on the discovery of an East Asian–specific BIM deletion polymorphism that mediates intrinsic resistance to tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML) and epidermal growth factor receptor (EGFR)-mutated non–small-cell lung cancer (EGFR NSCLC)2. Mechanistically, the BIM deletion results in the generation of BIM splice isoforms lacking the proapoptotic BH3 domain and is sufficient to cause partial, but not absolute, resistance to TKI monotherapy2. Further, BIM deletion–mediated TKI resistance can be overcome by increases in TKI concentration or the use of more potent TKIs (T.K.K., C.T.H.C., J.W.J. Huang, K.P. Ng & S.T.O., unpublished data). In their correspondence, Chen et al.1 evaluated the response of 220 Chinese patients with CML to imatinib. They found the frequency of the BIM deletion polymorphism to be 13.6% in patients (30/220) and that there was no difference between BIM deletion carriers and noncarriers in the clinical response to imatinib.

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Authors and Affiliations

  1. Cancer & Stem Cell Biology Signature Research Programme, Duke–National University of Singapore Graduate Medical School, Singapore

    S Tiong Ong, Charles T H Chuah & Tun Kiat Ko

  2. Department of Haematology, Singapore General Hospital, Singapore

    S Tiong Ong & Charles T H Chuah

  3. Department of Medical Oncology, National Cancer Centre, Singapore

    S Tiong Ong & Wan-Teck Lim

  4. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

    S Tiong Ong

  5. Cancer Therapeutics & Stratified Oncology, Genome Institute of Singapore, Singapore

    Axel M Hillmer

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  1. S Tiong Ong
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Correspondence to S Tiong Ong.

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Competing interests

S.T.O., C.T.H.C. and A.M.H. hold a National University of Singapore, Singapore Health Services Pte. Ltd. and the Agency for Science, Technology and Research, Singapore patent (BRC/P/06094/01/PCT) for a method to detect resistance to cancer therapy and guide therapy to overcome resistance.

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Ong, S., Chuah, C., Ko, T. et al. Reply: The BIM deletion polymorphism cannot account for intrinsic TKI resistance of Chinese individuals with chronic myeloid leukemia. Nat Med 20, 1090–1091 (2014). https://doi.org/10.1038/nm.3652

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