C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells

CCAAT/enhancer-binding protein beta (C/EBP beta), also known as nuclear factor-interleukin-6 (NF-IL6), is a transcription factor that plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBP beta show impaired generation of B lymphocytes. We show that C/EBP beta regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBP beta, whereas normal B cells and plasma cells had little or no detectable levels of C/EBP beta. Silencing of C/EBP beta led to down-regulation of transcription factors such as IRF4, XBP1, and BLIMP1 accompanied by a strong inhibition of proliferation. Further, silencing of C/EBP beta led to a complete down-regulation of antiapoptotic B-cell lymphoma 2 (BCL2) expression. In chromatin immunoprecipitation assays, C/EBP beta directly bound to the promoter region of IRF4, BLIMP1, and BCL2. Our data indicate that C/EBP beta is involved in the regulatory network of transcription factors that are critical for plasma cell differentiation and survival. Targeting C/EBP beta may provide a novel therapeutic strategy in the treatment of multiple myeloma. (Blood. 2009; 114: 3890-3898)