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  • Monograph from the Acute Leukemia Forum 1999 on Advances and Controversies in the Therapy of Acute Myelogenous Leukemia
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Novel mechanisms of drug resistance in leukemia

Leukemia volume 14, pages 467–473 (2000)Cite this article

Abstract

A key issue in the treatment of acute leukemia is the development of resistance to chemotherapeutic drugs. Several mechanisms may account for this phenomenon, including failure of the cell to undergo apoptosis in response to chemotherapy, or failure of the drug to reach and/or affect its intracellular target. This review focuses on the latter mechanism, and on intracellular drug transport resistance mechanisms in particular. Expression of the ATP-binding cassette (ABC) transporter P-glycoprotein (Pgp) has generally been reported to correlate with prognosis in acute myeloid leukemia (AML). Additionally, but more controversial, expression of the ABC transporter multidrug resistance protein (MRP) and the vault-transporter lung resistance protein (LRP) have been correlated with outcome in AML. Despite these findings, functional efflux assays indicate the presence of non-Pgp, non-MRP transporters in AML. Recently, a novel ABC transporter, breast cancer resistance protein (BCRP) was cloned and sequenced in our laboratory. Transfection and overexpression of BCRP in drug-sensitive cells confers drug-resistance to the cells. BCRP is a half-transporter, and may homodimerize or form heterodimers (with a yet unknown half-transporter) to produce an active transport complex. Relatively high expression of BCRP mRNA is observed in approximately 30% of AML cases, suggesting a potential role for this new transporter in drug resistance in leukemia.

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Acknowledgements

Dr Ross is supported in part by a Department of Veterans Affairs Merit Review Grant, by a Translational Research Award from the Leukemia Society of America, and by grant RO1-CA77545 from the National Cancer Institute, National Institutes of Health.

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  1. University of Maryland Greenebaum Cancer Center, Baltimore

    DD Ross

  2. Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore

    DD Ross

  3. Baltimore Veterans Medical Center, Baltimore, MD, USA

    DD Ross

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Ross, D. Novel mechanisms of drug resistance in leukemia. Leukemia 14, 467–473 (2000). https://doi.org/10.1038/sj.leu.2401694

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