EZH2 as a Potential Target in Diffuse Large B Cell Lymphoma

Ari Melnick, MD, a professor of medicine at the Weill Cornell Medical College, discusses EZH2 and its potential as a target in diffuse large B cell lymphoma (DLBCL).

Clinical Pearls:

• EZH2 is an epigenetic modifier protein that forms part of the so-called polycomb complex 2 that was found to be highly expressed in DLBCL
• Studies have shown that EZH2 functions to suppress checkpoints that stops cells from dividing
• EZH2 is frequently mutated in the GCB-type DLBCL tumors and in follicular lymphomas, supercharging the protein
• The mutation adds three methyl groups to the tails of histone 3 lysine 27, which causes the repression of proliferation checkpoint regulatory genes and genes involved in the differentiation of B cells
• The supercharged EZH2 blocks the ability of germinal center B cells to differentiate, causing the cells to continue to divide