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Minimal residual disease in acute myeloid leukemia is predicted by P-glycoprotein activity but not by multidrug resistance protein activity at diagnosis

Leukemia volume 17, pages 1674–1677 (2003)Cite this article

TO THE EDITOR

Although chemotherapy induces morphologic complete remission (CR) in most acute myeloid leukemia (AML) patients, many will eventually relapse due to the persistence and subsequent outgrowth of minimal residual disease (MRD). It has been reported that high MRD levels at follow-up and high P-glycoprotein (Pgp, ABCB1) activity at diagnosis correlate with shorter survival.1,2,3 This is less clear for other ABC-transporters such as multidrug resistance protein (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2).3 Based on our previous findings of homogeneous distribution of drug efflux capacity over the total blast population at diagnosis and the constancy of both Pgp, MRP1 and BCRP function during the course of disease, including MRD and relapse,4 we hypothesized that the emergence of MRD and its frequency at follow-up might be a direct resultant of the presence and level of activity of ABC-transporters at diagnosis. No study has been designed thus far to address this question directly, although preliminary evidence favoring this idea has been provided for Pgp:1,2 patients with high MRD levels after chemotherapy had higher Pgp expression/activity at diagnosis. No such studies have been performed for MRP1 and BCRP. Since we previously found that the majority of AML patients display Pgp and MRP1 activity at diagnosis, whereas BCRP activity was present in 3/26 patients only,4 we focused this study primarily on the ABC transporters Pgp and MRP1.

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Acknowledgements

We thank G Evertse, C Dekker-van Roessel, M Leidekker, C Eeltink, M Leissink and Y den Hartog for retrieving clinical patient's characteristics. J Pater and M van der Maas are acknowledged for technical assistance with the drug efflux experiments.

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Authors and Affiliations

  1. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    M A van der Pol, N Feller, G J Ossenkoppele, G W D Weijers, A H Westra, A van Stijn & G J Schuurhuis

  2. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

    H J Broxterman

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  1. M A van der Pol
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van der Pol, M., Feller, N., Ossenkoppele, G. et al. Minimal residual disease in acute myeloid leukemia is predicted by P-glycoprotein activity but not by multidrug resistance protein activity at diagnosis. Leukemia 17, 1674–1677 (2003). https://doi.org/10.1038/sj.leu.2403025

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