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 University of East Anglia Research Groups/Centres > Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Related URLs:	https://jhoonline.biomedcentral.com/arti...
Depositing User:	Pure Connector
Date Deposited:	30 May 2018 14:33
Last Modified:	30 May 2018 14:33
URI:	https://ueaeprints.uea.ac.uk/id/eprint/67244
DOI:	10.1186/s13045-018-0614-4

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