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Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Two main subgroups of DLBCL include germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Molecular profiling can further classify DLBCL into four subtypes: MCD (both CD79B and MYD88 L265P), BN2 (NOTCH2 mutation or BCL6 fusion), N1 (NOTCH1 mutation), or EZB (EZH2 mutation or BCL2 fusion). EZH2 inhibitors were recommended for patients with the EZB subtype of DLBCLs; however, little is known about the therapeutic mechanisms. Our results showed that DZNep arrested G1/S phase of GCB-DLBCL cells and inhibited the cell proliferation  in vitro  through upregulation of p16 by demethylating its promoter. These results suggest that DZNep may have potential as a novel therapeutic agent for DFLBL therapy. This agent may serve as a novel molecular agent to be applied to GCB DLBCL.

EZH2 inhibitor DZNep blocks cell proliferation of GCB-DLBCL cells by upregulating p16