Selective HDAC3 Inhibition Induces Apoptosis in B Cell Lymphoma through Protein Acetylation

Acetylation is a reversible process under the control of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Acetyl proteome analysis revealed that acetylation regulates various cellular processes through both histone and non-histone proteins (Choudhary et al., Science, 2008). Subsets of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) have inactivating mutations of HATs, CBP and p300 (Pasqualucci et al., Nature, 2011). In addition, p300 mutation is a poor prognostic factor in FL patients (Pastore et al., Lancet Oncol, 2015). In a mouse model, CBP deficiency promotes B cell lymphomagenesis through H3K27 deacetylation of enhancer mediated by the HDAC3, which forms repressor complex with Bcl-6, SMRT and NCoR (Jiang et al., Cancer Discov, 2016).Human HDACs consist of 18 isoenzymes that are classified into 4 classes (I-IV). Among the 4 classes, class I includes 4 HDACs (HDAC1, 2, 3 and 8) that are ubiquitous. Four HDAC inhibitors are FDA approved for the treatment of cutaneous T cell lymphoma (romidepsin, vorinostat), peripheral T cell lymphoma (belinostat) and multiple myeloma (panobinostat). These inhibitors mainly target class I and class II HDACs, each with a different specificity. This non-specific nature of current HDAC inhibitors limits their efficacy and causes adverse effects, therefore, several selective HDAC inhibitors has been developed. Selective HDAC3 inhibition restricts myeloma cell growth in vitro and in vivo more efficiently tha...
Source: Blood - Category: Hematology Authors: Tags: 622. Lymphoma Biology-Non-Genetic Studies: Poster I Source Type: research