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Breast cancer resistance protein (BCRP/ABCG2) does not confer resistance to gemtuzumab ozogamicin and calicheamicin-γ1 in acute myeloid leukemia cells

Leukemia volume 18, pages 1914–1917 (2004)Cite this article

TO THE EDITOR

Gemtuzumab ozogamicin (GO, Mylotarg™), a novel immunoconjugate therapy for acute myeloid leukemia (AML), consists of a humanized anti-CD33 antibody conjugated to a calicheamicin-γ1 derivative, N-acetyl gamma calicheamicin dimethyl hydrazine. After internalization, the cytotoxic moiety is released and activated to a highly reactive species that ultimately causes cell death.1 GO alone induces remissions in approximately 30% of adults with CD33+, relapsed AML.2 The mechanisms underlying GO resistance are incompletely understood; however, efflux of the calicheamicin moiety by P-glycoprotein (Pgp) and, to a lesser extent, multidrug resistance protein (MRP), has been implicated.3

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Acknowledgements

This work is supported in part by research funding from the Leukemia and Lymphoma Society (#7040-03), the National Cancer Institute (#CA92316), and the National Institutes of Health (#DK56465). RBW is a recipient of a fellowship from the Swiss Foundation for Medical-Biological Grants (#1098). H-PK is a Markey Molecular Medicine Investigator. IDB is a recipient of an FM Kirby/American Cancer Society Clinical Research Professorship.

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Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    R B Walter, B W Raden, J Thompson, D A Flowers, H-P Kiem, I D Bernstein & M L Linenberger

  2. Department of Medicine, University of Washington, Seattle, WA, USA

    H-P Kiem & M L Linenberger

  3. Department of Pediatrics, University of Washington, Seattle, WA, USA

    I D Bernstein

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  1. R B Walter
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  2. B W Raden
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  3. J Thompson
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  4. D A Flowers
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  5. H-P Kiem
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  6. I D Bernstein
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  7. M L Linenberger
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Correspondence to R B Walter.

Additional information

This work has been presented in part at the 45th annual meeting of the American Society of Hematology (December 6–9, 2003; San Diego, CA, USA; Blood 2003; 102: 208b–209b; abstract #4553)

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Walter, R., Raden, B., Thompson, J. et al. Breast cancer resistance protein (BCRP/ABCG2) does not confer resistance to gemtuzumab ozogamicin and calicheamicin-γ1 in acute myeloid leukemia cells. Leukemia 18, 1914–1917 (2004). https://doi.org/10.1038/sj.leu.2403461

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