Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal
cell-derived IL-6 via c-MYC
#MMPMID29769142
Piddock RE
; Marlein CR
; Abdul-Aziz A
; Shafat MS
; Auger MJ
; Bowles KM
; Rushworth SA
J Hematol Oncol
2018[May]; 11
(1
): 66
PMID29769142
show ga
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. CONCLUSIONS: Our presented findings show that MM-derived
MIF causes BMSC secretion of IL-6 and IL-8 via BMSC cMYC. Furthermore, we show
that the cMYC inhibitor JQ1 can reduce BMSC secreted IL-6 in vivo, irrespective
of tumor burden. These data provide evidence for the clinical evaluation of both
MIF and cMYC inhibitors in the treatment of MM.
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