Dr. Melnick on Targeting EZH2 in DLBCL

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).

Melnick says the epigenetic modifier protein EZH2 is an emerging target in DLBCL that has shown promise. This protein is highly expressed in DLBCL as well as in prostate and breast cancer tumors. Studies have shown that EZH2 suppresses checkpoints that stop cells from dividing. If EZH2 is inhibited in lymphoma cells, Melnick says, they will not be able to proliferate.

Other studies have shown that 30% of GCB-type DLBCL tumors and follicular lymphomas have a mutation in EZH2, which supercharges the protein to make it much stronger, Melnick says. The mutation adds three methyl groups to the tails of histone H3 lysine 27, which causes the repression of proliferation checkpoint regulatory genes and genes involved in the differentiation of B cells. Melnick says this supercharged EZH2 blocks the ability of germinal center B cells to differentiate, causing the cells to continue to divide.