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Response to ‘Overexpression of ABCB1 as prediction marker for CML: How close we are to translation into clinics?’

Leukemia volume 31, pages 769–770 (2017)Cite this article

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In our original study we postulated that clonal selection of ABCB1-expressing granulocytes contributed to the increased ABCB1 levels observed in patients from the high ABCB1-fold change group. Unfortunately, cell population data are not available for day 22, so we are unable to ascertain changes in the percentage of granulocytes (basophils, eosinophils, neutrophils) in response to imatinib therapy. We observed that, at day 1, the majority of patients tended to express two populations of granulocytes regardless of the ABCB1-fold rise group to which they belonged: ABCB1-positive and ABCB1-negative. Conversely, at day 22, patients with a high fold rise in ABCB1 mRNA were more likely to harbour ABCB1-positive granulocytes, while in patients with a low fold rise in ABCB1 mRNA the ABCB1-negative granulocyte population had increased. Thus, we hypothesised that the change in ABCB1 occurred via clonal selection of ABCB1-expressing granulocytes in the case of high-fold-rise patients, rather than ABCB1 upregulation. However, these data do not provide any information about the relative numbers of granulocytes between the two patient groups.

Importantly, we observed that lymphocytes and monocytes express negligible levels of ABCB1 at day 1 and day 22 in patients from both low and high ABCB1-fold rise groups.2 Thus it is unlikely that these cell types influence changes in overall ABCB1 expression levels. Conversely, the alterations in ABCB1 expression observed at the two time points were attributable to ABCB1 expressed on granulocytes and we observed no difference in percentage of basophils, eosinophils or neutrophils between low- and high-fold-rise ABCB1 patients.

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References

  1. Nemethova V, Razga F . Overexpression of ABCB1 as prediction marker for CML: How close we are to translation into clinics? Leukemia, e-pub ahead of print 21 October 2016 doi:10.1038/leu.2016.266.

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  2. Eadie LN, Dang P, Saunders VA, Yeung DT, Osborn MP, Grigg AP et al. The clinical significance of ABCB1 overexpression in predicting outcome of CML patients undergoing first-line imatinib treatment. Leukemia, e-pub ahead of print 15 July 2016 doi:10.1038/leu.2016.179.

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Authors and Affiliations

  1. Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia

    L N Eadie, T P Hughes & D L White

  2. Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    L N Eadie, T P Hughes & D L White

  3. Division of Haematology, SA Pathology, Adelaide, South Australia, Australia

    T P Hughes

  4. Department of Paediatrics, University of Adelaide, Adelaide, South Australia, Australia

    D L White

Authors
  1. L N Eadie
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  2. T P Hughes
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  3. D L White
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Correspondence to D L White.

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Competing interests

TPH and DLW receive honoraria and research funds from Novartis Pharmaceuticals, and are members of Advisory Boards for Novartis. TPH is a chair of the CML/MPN disease group for the Australasian Leukaemia and Lymphoma Group (ALLG). Neither Novartis nor ALLG had roles in the design of the study, collection and analysis of the data or the decision to publish. LNE declares no conflict of interest.

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Eadie, L., Hughes, T. & White, D. Response to ‘Overexpression of ABCB1 as prediction marker for CML: How close we are to translation into clinics?’. Leukemia 31, 769–770 (2017). https://doi.org/10.1038/leu.2016.335

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