Histone deacetylase inhibitors activate CIITA and MHC class II antigen expression in diffuse large B‐cell lymphoma

• DOI: 10.1111/imm.12136
• Publication Date: 2013-06-21T14:25:31Z
• Authors: Kelly A. Cycon; Kathleen Mulvaney; Lisa M. Rimsza; Daniel Persky; Shawn P. Murphy
• Keywords: CIITA

Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin's (NHL) diagnosed in USA, consists at least two distinct subtypes: germinal centre B (GCB) and activated (ABC). Decreased MHC class II (MHCII) expression on tumours both DLBCL subtypes directly correlates with significant decreases patient survival. One mechanism accounting for MHCII down-regulation is reduced transactivator (CIITA), master regulator transcription. Furthermore, CIITA ABC presence transcriptional repressor positive regulatory domain-I-binding factor-1 (PRDI-BF1). However, mechanisms underlying GCB are currently unclear. In this study, we demonstrate that neither PRDI-BF1 nor CpG hypermethylation promoters responsible decreased DLBCL. contrast, histone modifications associated an open chromatin conformation active transcription were significantly lower CIITA(-) cells compared CIITA(+) cells, which suggests epigenetic contribute to repression Treatment or CIITA(low) several different deacetylase inhibitors (HDACi) modest expression. levels higher these after exposure HDAC-1-specific inhibitor MS-275. These results suggest repressed through involving HDACs, HDACi treatment can alleviate repression. observations may have important implications therapy.