Myeloma-derived macrophage inhibitory factor regulates bone marrow stromal cell-derived IL-6 via c-MYC.
J Hematol Oncol
; 11(1): 66, 2018 05 16.
Article
en En
| MEDLINE
| ID: mdl-29769142
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. 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células de la Médula Ósea
/
Factores Inhibidores de la Migración de Macrófagos
/
Interleucina-6
/
Células del Estroma
/
Oxidorreductasas Intramoleculares
/
Mieloma Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Hematol Oncol
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido