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Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia

Leukemia volume 15, pages 1554–1563 (2001)Cite this article

Abstract

Relapse is common in acute myeloid leukemia (AML) due to persistence of residual leukemia cells: minimal residual disease (MRD). In 102 out of 127 patients (80%), cells at diagnosis displayed one or more leukemia-associated phenotypes (LAP), ie combinations of cell surface markers which are absent in normal cells and can thus be used to detect MRD at follow-up. Functional characterization of MRD cells for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) activity is essential to investigate the role of these drug transport proteins in multidrug resistance in AML. A fluorescent probe assay using Syto16/PSC833 and calcein-AM/probenecid as substrate/ modulator of the Pgp and MRP pump, respectively, and subsequent labeling of cells with monoclonal antibodies for LAP detection allowed simultaneous detection of LAP and Pgp or MRP activity. Validation of this assay is shown for 30 newly diagnosed AML and 11 MRD situations. In addition, no significant differences were found when comparing fresh and cryopreserved de novo AML for LAP expression (n = 43), Pgp (n = 30) and MRP (n = 24) function and for MRD samples for simultaneous LAP expression and Pgp/MRP activity (n = 10). This approach enables longitudinal and multicenter studies on the detection, quantification and functional characterisation of MRD cells.

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Authors and Affiliations

  1. Department of Hematology, Medical Center Vrije Universiteit, Amsterdam, The Netherlands

    MA van der Pol, JM Pater, N Feller, AH Westra, A van Stijn, GJ Ossenkoppele & GJ Schuurhuis

  2. Department of Medical Oncology, Medical Center Vrije Universiteit, Amsterdam, The Netherlands

    HJ Broxterman

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van der Pol, M., Pater, J., Feller, N. et al. Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia. Leukemia 15, 1554–1563 (2001). https://doi.org/10.1038/sj.leu.2402245

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