Epigenetic modifying compounds (EMC) have recently emerged as therapeutic agents for the treatment of haematological malignancies and have been shown to modulate the immune response. Despite the extensive studies on EMC, the precise functional role of these compounds is poorly understood. This is especially true with regards to context-dependent effects in different cell types. To date, the dogma of EMC such as histone deacetylase inhibitors (HDACi) is that they are global regulators of gene expression. Thus, their biological effects are believed to be relatively promiscuous and dissecting their mechanisms has been problematic.

Recently, we studied how EMC can be used to modulate healthy immune cells and demonstrated that their biological effects are extremely predictable and have the potential to be utilized in both a compound and cell-type specific manner. Using quantitative in vitro studies, we dissected the effects of different EMC, including the HDACi Panobinostat, Vorinostat and Romidepsin on B cell response. By combining quantitative analysis with epigenetic analysis via ChIP-Seq and RNA-Seq, in some instances, we could assign the function of EMC in healthy immune cells to a single gene that regulated parameters of B cell function including proliferation, survival and differentiation.

With this information, we will be able to use epigenetic modification to specifically target B cell function in pathological situations such as autoimmunity and immunodeficiency. Furthermore, this information will aid in managing poorly understood side effects for current EMC therapies in blood cancers.