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Anti-oxidant vitamin E prevents accumulation of imatinib-resistant BCR-ABL1 kinase mutations in CML-CP xenografts in NSG mice

Leukemia volume 27, pages 2253–2254 (2013)Cite this article

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Chronic myeloid leukemia in chronic phase (CML-CP) is initiated by t(9;22), which encodes p210BCR-ABL1 tyrosine kinase that transforms hematopoietic stem cells.1 CML-CP is leukemia stem cells (LSCs)-derived but leukemia progenitor cell (LPCs)-driven disease. In CML-CP patients ABL1 tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib and nilotinib, may induce complete cytogenetic or even molecular responses (CCR and CMR, respectively), but it is unlikely that they will cure CML.2 One of the major reasons of that are BCR-ABL1 tyrosine kinase mutations.3 These TKI-resistant BCR-ABL1 kinase isoforms usually result from point mutations in the fragment encoding the kinase domain, and numerous strategies have been tested to avoid and overcome the resistance.4

Pre-existing and acquired point mutations in BCR-ABL1 kinase are detected in ∼23% of imatinib-naive and 50–90% of imatinib-resistant CML-CP patients, respectively.3 Moreover, BCR-ABL1 kinase mutants resistant to second- and third-generation TKIs emerged, for example due to new and/or compound mutations.5, 6 Thus, CML cells are elusive targets even for the most advanced TKI therapies due to continuous accumulation of point mutations in BCR-ABL1 kinase, which encode the resistance to next generations of TKIs.7

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Acknowledgements

MN-S and GH share equal contribution. This work was supported by NIH/NCI CA123014 and CA134458 to T Skorski, N401 039037 from the Polish Ministry of Education and Science to G Hoser and EU program: FP7-REGPOT-2012-CT2012-316254-BASTION to T Stoklosa.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA

    M Nieborowska-Skorska & T Skorski

  2. Department of Clinical Cytology, Medical Center for Postgraduate Education, Warsaw, Poland

    G Hoser

  3. Abteilung Haematologie/Onkologie, Universitaetsklinikum Jena, Jena, Germany

    A Hochhaus

  4. Department of Immunology, Medical University of Warsaw, Warsaw, Poland

    T Stoklosa

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  1. M Nieborowska-Skorska
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  2. G Hoser
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Correspondence to T Skorski.

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Nieborowska-Skorska, M., Hoser, G., Hochhaus, A. et al. Anti-oxidant vitamin E prevents accumulation of imatinib-resistant BCR-ABL1 kinase mutations in CML-CP xenografts in NSG mice. Leukemia 27, 2253–2254 (2013). https://doi.org/10.1038/leu.2013.123

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