Our data point to a direct role for both Aurora‐A and MDM2 in SETD2‐enhanced proteasome‐mediated degradation in advanced‐phase CML: Aurora‐A can be hypothesized to provide the phosphorylation signals triggering MDM2‐mediated hyper‐ubiquitination of SETD2. This evidence concerns the gene MDM2 and chronic myelogenous leukemia, BCR-ABL1 positive.