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Targeting the BAFF/APRIL Cytokine Network in Multiple Myeloma

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Advances in Biology and Therapy of Multiple Myeloma

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Abstract

The BAFF/APRIL cytokine network is intimately linked through three different receptors to the survival and fitness of B lineage cells, from the first expression of a complete B cell receptor to their differentiation to memory B and plasma cells. The specific, pervasive, and survival-linked nature of the relationship between B lineage cells and this cytokine network make it both a likely disease modifier and a tantalizing target for therapeutic intervention in humoral immune pathologies. Some current therapeutics directly targeting the BAFF/APRIL cytokine network have been developed and undergone clinical trials in the context of autoimmunity with some limited success. Despite a powerful rationale and a constantly deepening mechanistic understanding of the BAFF/APRIL cytokine network in normal and malignant plasma cells, trials of cytokine network-targeted therapeutics in multiple myeloma are still in their infancy and have shown only minor promise. There is significantly greater potential in inhibiting NF-kB, a downstream mediator of BAFF/APRIL signals.

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Acknowledgments

This work was supported by National Institutes of Health Grants CA105258 and CA062242 (to D.F.J.). We would also like to thank the numerous investigators whose work informed the review, but whose work was not specifically cited due to space constraints.

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Authors and Affiliations

  1. Department of Immunology, Mayo Graduate School, Mayo Clinic, Rochester, MN, 55905, USA

    Stephen A. Mihalcik

  2. Department of Immunology, Guggenheim 4, Mayo Clinic, College of Medicine, 200 First Street Southwest, Rochester, MN, 55905, USA

    Diane F. Jelinek Ph.D.

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  1. Stephen A. Mihalcik
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  2. Diane F. Jelinek Ph.D.
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Correspondence to Diane F. Jelinek Ph.D. .

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  1. Dana-Farber Cancer Institute, Harvard Medical School, Binney St. 44 44, Boston, 02115, Massachusetts, USA

    Nikhil C. Munshi

  2. Dana-Farber Cancer Institute, Dept. Medical Oncology, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    Kenneth C. Anderson

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Mihalcik, S.A., Jelinek, D.F. (2013). Targeting the BAFF/APRIL Cytokine Network in Multiple Myeloma. In: Munshi, N., Anderson, K. (eds) Advances in Biology and Therapy of Multiple Myeloma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4666-8_10

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