A proto-oncogene BCL6 is up-regulated in the bone marrow microenvironment in multiple myeloma cells

Teru Hideshima, Constantine Mitsiades, Hiroshi Ikeda, Dharminder Chauhan, Noopur Raje, Gullu Gorgun, Hiromasa Hideshima, Nikhil C. Munshi, Paul G. Richardson, Daniel R. Carrasco, Kenneth C. Anderson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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-α (TNF-α) also triggered Bcl-6, but independently of STAT3, whereas IκB kinaseβ inhibitor down-regulated TNF-α-induced Bcl-6, indicating that the canonical nuclear factor-κB pathway mediates TNF-α-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-κB pathways and that targeting Bcl-6, either directly or via these cascades, inhibits MM cell growth in the BM milieu.

Original languageEnglish (US)
Pages (from-to)3772-3775
Number of pages4
JournalBlood
Volume115
Issue number18
DOIs
StatePublished - May 6 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Hideshima, T., Mitsiades, C., Ikeda, H., Chauhan, D., Raje, N., Gorgun, G., Hideshima, H., Munshi, N. C., Richardson, P. G., Carrasco, D. R., & Anderson, K. C. (2010). A proto-oncogene BCL6 is up-regulated in the bone marrow microenvironment in multiple myeloma cells. Blood, 115(18), 3772-3775. https://doi.org/10.1182/blood-2010-02-270082