EZH2 and acute myeloid leukemia: This is especially enlightening as multiple groups have now discovered decreases in EZH2 protein levels to be a nongenetic resistance mechanism to some AML therapies, including chemotherapy and FLT3 inhibition, indicating that combination with EZH2/PRC2 inhibitors may be beneficial.95,96 This also indicates that EZH2 may have noncanonical functions in the leukemic setting beyond its histone methyltransferase activity (Figure 2C).