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Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function

Leukemia volume 18, pages 1252–1257 (2004)Cite this article

Abstract

Data on breast cancer resistance protein (BCRP, MXR, ABCG2) expression in acute myeloid leukemia (AML) have been inconsistent, possibly due to use of different assays in different studies. BCRP mRNA was studied by the reverse-transcription polymerase chain reaction and BCRP protein expression (BXP-21, BXP-34 or anti-ABCG2 antibody, with anti-CD34 and anti-CD33) and function (fumitremorgin C modulation of mitoxantrone retention) by flow cytometry in eight cell lines and in pretreatment blasts from 31 AML patients. BCRP mRNA levels, antibody staining and function correlated strongly in cell lines (Pearson r values, 0.73–0.97), but not in AML samples. AML sample BCRP mRNA levels were between those in parental 8226 and 35-fold mitoxantrone-resistant 8226/MR20 cells in all but one case, and BCRP mRNA had the wild-type sequence at codon 482 in all. In AML, unlike in cell lines, BCRP protein expression or function, when present, was only detected in small subpopulations. BCRP mRNA and protein expression did not correlate, nor did staining with different BCRP antibodies, and function did not correlate with mRNA nor protein expression. Presence of BCRP only in subpopulations and discordance among BCRP measurements suggest complex biology of BCRP in AML and incomplete modeling by cell lines.

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Acknowledgements

Supported by Grants R21 CA 098457 and R21 CA 89938 from the National Cancer Institute (to MRB), a Leukemia and Lymphoma Society Translational Research Program grant (to MRB), a Department of Veterans Affairs Merit Review Grant (to DDR), a grant from Pharmacia Oncology and the Cancer and Leukemia Group B Foundation (to AS), shared resources of the Roswell Park Cancer Center Support Grant (P30 CA16056), the Leonard S LoVullo Memorial Fund for Leukemia Research and the Dennis J Szefel, Jr Endowed Fund for Leukemia Research at Roswell Park Cancer Institute.

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Author notes

  1. A Suvannasankha

    Present address: Hematology/Oncology Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

Authors and Affiliations

  1. Department of Medicine, Leukemia Section, Roswell Park Cancer Institute, Buffalo, NY, USA

    A Suvannasankha, H Minderman, K L O'Loughlin & M R Baer

  2. Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    T Nakanishi & D D Ross

  3. Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA

    W R Greco

  4. Baltimore Department of Veterans Affairs Medical Center, Baltimore, MD, USA

    D D Ross

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  1. A Suvannasankha
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Correspondence to M R Baer.

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Suvannasankha, A., Minderman, H., O'Loughlin, K. et al. Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function. Leukemia 18, 1252–1257 (2004). https://doi.org/10.1038/sj.leu.2403395

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