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  • Letter to the Editor
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Reply to Zong et al.

Leukemia volume 21, pages 1563–1564 (2007)Cite this article

The arguments presented by Zong et al.1, 2 on the controversial role of P-glycoprotein (P-gp) are relevant. We agree that there is no evidence at present that this transporter represents per se a major resistance factor in vivo. In fact, in our recent clinical study we have shown that the MDR1 (ABCB1) 3435C>T polymorphism, associated with altered P-gp expression, tends to influence imatinib systemic pharmacokinetics, albeit not significantly.3 P-gp probably contributes to resistance but is not solely responsible for that.

The various transporters involved in imatinib systemic, tissular and cellular disposition are characterized by competing and/or opposite effects. Focusing thus only on efflux transporters (i.e. ABCB1 and ABCG2) in in vitro cell systems certainly provides an incomplete picture of the complex and delicate influx- and efflux-balance existing in vivo. However, an indirect and important finding of our in vitro experiments, in which MDR1 expression and function has been specifically silenced by RNAi, was that they allow to reveal the remarkable accumulation of imatinib in cells. This suggests an important role for influx drug transporters on imatinib cellular disposition.4 Influx transporters – such as human organic transporter 1 – may indeed also contribute to influence imatinib clinical response, as suggested by Thomas et al.5 and observed by Crossman et al.6 in patients with chronic myeloid leukemia.

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References

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Authors and Affiliations

  1. Division of Clinical Pharmacology, University Hospital Center and University of Lausanne, Switzerland

    N Widmer, A Fayet, T Buclin & L A Decosterd

  2. Department of Hematology and Oncology, Laboratory of Molecular Genetics, Medical University Innsbruck, Austria

    H Rumpold

  3. Department of Hematology and Oncology, Laboratory of Tumorbiology and Angiogenesis, Medical University Innsbruck, Austria

    G Untergasser

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  1. N Widmer
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  2. H Rumpold
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  3. G Untergasser
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  4. A Fayet
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  5. T Buclin
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  6. L A Decosterd
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Widmer, N., Rumpold, H., Untergasser, G. et al. Reply to Zong et al.. Leukemia 21, 1563–1564 (2007). https://doi.org/10.1038/sj.leu.2404674

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