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Evaluating surface erythropoietin receptor in multiple myeloma

Leukemia volume 26, pages 1883–1886 (2012)Cite this article

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Anemia is common in cancer patients and is especially frequent in myeloma patients because of the high prevalence of renal insufficiency. Although erythropoietin (Epo) can reduce the need for blood transfusions, its use has been tempered by adverse effects on venous thromboembolism, tumor progression, and cancer survival in recent clinical trials.1 Although some myeloma patients were included in these trials, no prospective study has evaluated the effect of Epo on survival in myeloma. Epo use was associated with significantly reduced myeloma survival in one retrospective study,2 whereas other studies showed that Epo caused myeloma regression in mice,3 that Epo did not impair time to progression or overall survival in patients treated with melphalan and prednisone with or without bortezomib,4 or that Epo improved survival.5

Whether tumor epithelial and/or endothelial cells express functional Epo receptor (EpoR) is the subject of controversy.6 The ability to unequivocally link tumor EpoR expression with Epo treatment and clinical outcomes would provide a means for directly testing the clinical significance of tumor EpoR expression. Although EpoR mRNA levels can be reliably measured in formalin-fixed, paraffin-embedded tumor tissue,7 the detection of EpoR protein in these specimens using immunohistochemistry has been confounded by the low level of EpoR protein and by inadequate antibody specificity.8 Using a sensitive and specific monoclonal antibody (A82), and semi-quantitative western blotting with whole-cell lysates, scientists at Amgen recently demonstrated absence or low expression of EpoR protein (<100 EpoR dimers per cell) in 54 human tumor cell lines, whereas 7 other non-erythroid cell lines expressed between 400 and 3200 EpoR dimers per cell.9 However, this study did not examine EpoR levels in myeloma cell lines or primary tumor cells.

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Acknowledgements

This work was supported by the National Institutes of Health (1R01CA135357 to CAB) and the American Cancer Society (117682-MRSG-09-268-01-CCE to CPM). We thank Greg Levin and Megan Wilson for clinical flow cytometry, Dr Steven Elliott for A82, and Dr Harvey Lodish for insightful discussions.

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Authors and Affiliations

  1. Department of Medicine/Hematology and the Institute for Stem Cell and Regenerative Medicine, Seattle, WA, USA

    C P Miller, K Rattray, Y Zhang, N Burwick, S Chien, C A Blau & P S Becker

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

    B L Wood

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

    W I Bensinger

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  1. C P Miller
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Correspondence to P S Becker.

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Miller, C., Rattray, K., Zhang, Y. et al. Evaluating surface erythropoietin receptor in multiple myeloma. Leukemia 26, 1883–1886 (2012). https://doi.org/10.1038/leu.2012.58

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