Prior preclinical studies have shown that pevonedistat and AZA both upregulate NOXA,which competes with effector molecules at the BH3 binding-site of MCL1 and inhibitsits anti-apoptotic function allowing for activation of BAX/BAK and subsequentapoptosis.75, –77 It wasrecently demonstrated that pevonedistat combined with AZA synergistically inducesNOXA expression more than either single agent alone in AML cells. This evidence concerns the gene MCL1 and acute myeloid leukemia.