Histone acetylation as a therapy target in B-cell malignancies

Gene expression is regulated through the multilayer cellular mechanism, of which epigenetics is thought to have a significant impact. Cross-talk between epigenetic mechanisms such as DNA methylation, non-coding RNAs, and histone methylation/acetylation controls a cell's destiny. Protein acetylation is the most studied histone modification. Precise regulation of this posttranslational modification is vital for appropriate gene expression. Unlike histone methylation, acetylation has a significant impact on the physical properties of the nucleosome, weakening the interaction between DNA and histones. As a result, less dense chromatin conformation is present, allowing further transcription regulation. Due to the high impact on gene regulation, cancer cells can modify histone acetylation homeostasis for their own good. B-cell lymphomas, originating from B-cells at different stages of development include mature B-cell neoplasms, Hodgkin lymphomas, and plasma cell neoplasms such as multiple myeloma, diffuse large B-cell lymphoma, mantle lymphoma, and follicular lymphoma. These distinct pathologies share some common genetic and epigenetic abnormalities that can serve as an “anchor” for therapies. The protein machinery controlling histone acetylation can be altered to benefit patients. Although many preclinical studies are ongoing, aiming for a better understanding of histone acetylation, only a few small-molecule inhibitors have reached clinical trial testing in humans. Here, we summarize and discuss selected clinically tested histone acetylation modifiers in B-cell malignancies.