HDAC Inhibition Effectively Induce Apoptosis in Diffuse Large B Cell Lymphoma with High Bfl-1

Venetoclax, a Bcl-2 specific inhibitor, shows potential benefit in certain patients with diffuse large B cell lymphoma (DLBCL) when combined with conventional cytotoxic chemotherapy. However, both de novo and acquired resistance to venetoclax is frequently observed in DLBCL and endogenous Bfl-1 expression can render DLBCL insensitive to venetoclax. Given the difficulties for direct inhibition of Bfl-1, we looked for the indirect inhibitory strategies for Bfl-1 at both transcriptional and post-translational levels. Accordingly, we decided to use a pan-histone deacetylase (HDAC) inhibitor to decrease a Bfl-1 transcriptional factor, Wilms' tumor-1 (Wt-1), while increasing Noxa, an inactivating Bfl-1 binding partner in DLBCL.