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. The gene discussed is BAX; the disease is acute myeloid leukemia.