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P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are induced by arsenic trioxide (As2O3), but are not the main mechanism of As2O3-resistance in acute promyelocytic leukemia cells

Leukemia volume 17, pages 648–650 (2003)Cite this article

TO THE EDITOR

Trioxide (As2O3) represents a great advance in the management of patients with relapsed or refractory acute promyelocytic leukemia (APL). However, As2O3 resistance has been reported at diagnosis or as arising during treatment with As2O3 in some cases. Several investigators have studied the mechanisms of As2O3-resistance, and reported an alteration of cellular glutathione levels and the involvement of drug efflux pumps such as MDR-associated protein (MRP) and P-glycoprotein (P-gp).1,2 In some reports, drug-resistance modifiers restored the intracellular accumulation of As2O3.2,3,4 Therefore, As2O3 might also be affected by these transportation systems, and intracellular accumulation of As2O3 may be decreased in As2O3-resistant APL cells. In this study, we aimed to clarify the relation between these drug-resistance mechanisms and As2O3-resistance in APL cells. We also assessed the intracellular accumulation of As2O3 in APL cell lines and blast cells from patients with APL cells, because this has not been analyzed previously from the viewpoint of As2O3-resistance in APL.

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Authors and Affiliations

  1. Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu, Japan

    A Takeshita, K Shinjo, K Naito, H Matsui, K Shigeno, S Nakamura & K Ohnishi

  2. Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    A Takeshita, T Horii & M Maekawa

  3. Infection Diseases, Nagoya University, Nagoya, Japan

    K Kitamura & T Naoe

  4. Aichi Cancer Center, Nagoya, Japan

    R Ohno

Authors
  1. A Takeshita
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  2. K Shinjo
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  3. K Naito
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  4. H Matsui
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  5. K Shigeno
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  6. S Nakamura
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  8. M Maekawa
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  9. K Kitamura
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  10. T Naoe
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  11. K Ohnishi
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Takeshita, A., Shinjo, K., Naito, K. et al. P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are induced by arsenic trioxide (As2O3), but are not the main mechanism of As2O3-resistance in acute promyelocytic leukemia cells. Leukemia 17, 648–650 (2003). https://doi.org/10.1038/sj.leu.2402851

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  • DOI: https://doi.org/10.1038/sj.leu.2402851

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