Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC

Piddock, Rachel E., Marlein, Christopher R., Abdul-Aziz, Amina, Shafat, Manar S., Auger, Martin J., Bowles, Kristian M. and Rushworth, Stuart A. (2018) Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC. Journal of Hematology & Oncology, 11. ISSN 1756-8722

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Abstract

Multiple myeloma (MM) remains an incurable malignancy despite the recent advancements in its treatment. The protective effects of the niche in which it develops has been well documented; however, little has been done to investigate the MM cell’s ability to ‘re-program’ cells within its environment to benefit disease progression. Here, we show that MM-derived macrophage migratory inhibitory factor (MIF) stimulates bone marrow stromal cells to produce the disease critical cytokines IL-6 and IL-8, prior to any cell-cell contact. Furthermore, we provide evidence that this IL-6/8 production is mediated by the transcription factor cMYC. Pharmacological inhibition of cMYC in vivo using JQ1 led to significantly decreased levels of serum IL-6—a highly positive prognostic marker in MM patients.

Item Type: Article
Uncontrolled Keywords: myeloma,mif,cmyc,bmsc,stromali,l-6i,l-8,bone marrow
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: Pure Connector
Date Deposited: 30 May 2018 17:30
Last Modified: 22 Apr 2020 06:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/67250
DOI: 10.1186/s13045-018-0614-4

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