Thus, dual inhibition of MDM2/4 in primary DNMT3AWT/R882H/NPM1WT/p.W288Xfs*12 AML cells caused cell cycle arrest through upregulation of p53 target genes, in particular p21 and GADD45a, which resulted in growth retardation in vitro. Here, GADD45A is linked to acute myeloid leukemia.