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Multiple myeloma gammopathies

Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

Leukemia volume 33, pages 2695–2709 (2019)Cite this article

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Abstract

IL-6 signaling plays a crucial role in the pathogenesis of a number of diseases, including multiple myeloma, primary amyloidosis, cytokine release syndrome and other inflammatory conditions. It is central for the growth and survival of malignant plasma cells. IL-6R and IL-6ST receptors transduce IL-6 signaling. Molecular mechanisms regulating expression of IL-6R are not well understood and current therapies are based on monoclonal antibody to target IL-6 signaling. Small molecule inhibitors targeting IL-6 signaling are highly desirable. Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a. This is a novel finding and adds to existing therapies targeting IL-6 signaling.

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Acknowledgements

We would like to thank the estate of R. Staberg through the Department of Development at Mayo Clinic that supported some of this work. The primary multiple myeloma cell bank at Mayo Clinic is supported by the SPORE: CA186781, The Predolin Foundation and The JABBS Foundation.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA

    Ameet K. Mishra & David Dingli

  2. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA

    David Dingli

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Correspondence to David Dingli.

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Mishra, A.K., Dingli, D. Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells. Leukemia 33, 2695–2709 (2019). https://doi.org/10.1038/s41375-019-0470-4

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