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Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML)

Leukemia volume 16, pages 833–839 (2002)Cite this article

Abstract

Expression of the multidrug resistance proteins P-glycoprotein, encoded by the MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance-related protein or major vault protein (LRP/MVP) is associated with clinical resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical AML samples from diagnosis and relapse or refractory disease, using quantitative Taqman analysis. In addition, standard assays for P-glycoprotein expression and function were performed. BCRP was the only resistance protein that was expressed at a significantly higher RNA level (median 1.7-fold, P = 0.04) at relapsed/refractory state as compared to diagnosis. In contrast, LRP/MVP mRNA expression decreased as disease evolved (P = 0.02), whereas MDR1 and MRP1 mRNA levels were not different at relapse as compared to diagnosis. Also, at the protein level no difference of MDR1 between diagnosis and relapse was found. A significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P = 0.04). The present results suggest that BCRP, but not MDR1, MRP1 or LRP/MVP is associated with clinical resistant disease in AML.

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Acknowledgements

This study was supported by grants of the Sophia Foundation for Medical Research (SSWO grant 246), the Foundation Pediatric Oncology Center Rotterdam (Stichting SKOR), and the Kröger Society.

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Authors and Affiliations

  1. Department of Hematology, University Hospital, and Erasmus University, Rotterdam, The Netherlands

    MM van den Heuvel-Eibrink, EAC Wiemer, A Prins, PJM Vossebeld & P Sonneveld

  2. Department of Pediatric Oncology/Hematology, Sophia Children's Hospital, and Erasmus University, Rotterdam, The Netherlands

    MM van den Heuvel-Eibrink, JPP Meijerink & R Pieters

  3. Department of Statistics, University Hospital, Daniel den Hoed Cancer Centre, and Erasmus University, Rotterdam, The Netherlands

    B van der Holt

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van den Heuvel-Eibrink, M., Wiemer, E., Prins, A. et al. Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). Leukemia 16, 833–839 (2002). https://doi.org/10.1038/sj.leu.2402496

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