They also found that dual targeting of EZH1 and EZH2 is better able to deplete the LSC pool compared with targeting EZH2 alone.91 This is likely due to known compensation mechanisms between EZH2 and EZH1 in catalyzing H3K27 tri-methylation in hematopoietic cells.92,93 These preclinical data led to the use of the dual EZH1/2 inhibitor valemetostat as a single agent in a Phase 1 clinical trial in AML and ALL (NCT03110354, Table 2), but this trial was terminated prematurely due to slow enrollment. The gene discussed is EZH1; the disease is acute myeloid leukemia.