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

Rachel E. Piddock, Christopher R. Marlein, Amina Abdul-Aziz, Manar S. Shafat, Martin J. Auger, Kristian M. Bowles, Stuart A. Rushworth

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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.
Original languageEnglish
Article number66
JournalJournal of Hematology & Oncology
Volume11
DOIs
Publication statusPublished - 16 May 2018

Keywords

  • Myeloma
  • MIF
  • cMYC
  • BMSC
  • StromalI
  • L-6I
  • L-8
  • Bone marrow

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