MDM4 and acute myeloid leukemia: AML with FLT3-ITD mutations is highly associated with wtp53 dysfunction via additional different ways such as MDM2/MDM4 overexpression [11] (Supplementary Fig. 1), SIRT1 overexpression (resulting p53 deacetylation), PI3K/AKT pathway activation (promoting MDM2-mediated p53 degradation), STAT/MAPK pathway activation with BCL2 accumulation (opposing p53 activity), disturbing the nucleocytoplasmic shuttling of p53 [10], dysregulation of NPM (in patients with FLT3-ITD and NPM1 mutant) [12], and aberrant expression of certain miRNAs (e.g., miR-125b) [13].