Journal
BLOOD
Volume 115, Issue 18, Pages 3772-3775Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-02-270082
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Funding
- National Institutes of Health [CA10070, PO-1 78378, RO-1 CA50947]
- Multiple Myeloma Research Foundation
- LeBow Family Fund
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Constitutive B-cell lymphoma 6 (Bcl-6) expression was undetectable in multiple myeloma (MM) cell lines, except U266 cells. However, it was up-regulated by coculture with bone marrow (BM) stromal cell-culture supernatant (SCCS). Bcl-6 expression in patient MM cells in the BM was positive. Anti-interleukin-6 (IL-6)-neutralizing antibody significantly blocked SCCS-induced Bcl-6 in MM cells. Indeed, IL-6 strongly triggered Bcl-6 expression in MM cells, whereas Janus kinase inhibitor and STAT3 siRNA down-regulated Bcl-6. Tumor necrosis factor-alpha (TNF-alpha) also triggered Bcl-6, but independently of STAT3, whereas I kappa B kinase beta inhibitor down-regulated TNF-alpha-induced Bcl-6, indicating that the canonical nuclear factor-kappa B pathway mediates TNF-alpha-induced Bcl-6 expression. Importantly, down-regulation of Bcl-6 by shRNA significantly inhibited MM cell growth in the presence of SCCS. Our results therefore suggest that Bcl-6 expression in MM cells is modulated, at least in part, via Janus kinase/STAT3 and canonical nuclear factor-kappa B pathways and that targeting Bcl-6, either directly or via these cascades, inhibits MM cell growth in the BM milieu. (Blood. 2010; 115(18):3772-3775)
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