A protective function against TOP2‐targeting drugs in transformed HPS cells, as exemplified in our current study with various other cancer cell models, as well as the HMGA2‐mediated protection against DNA synthesis inhibitors such as HU (Ahmed et al., 2019; Yu et al., 2014), could therefore be critical factors for the increased occurrence of AML relapse. Here, HMGA2 is linked to acute myeloid leukemia.