TOP2A and cancer: With more than 60% of AML patients succumbing to leukemia‐related issues, and with high HMGA2 expression correlating to poor survival in both the experimental and validation groups (Marquis et al., 2018), we postulate here that resistance to treatment is, at least in part, due to both HMGA2's ability to catalytically activate TOP2A and to serve as replication fork chaperone during induced replication stress using DNA synthesis inhibitors; the latter role for HMGA2 has been demonstrated previously in other cancer cell models (Ahmed et al., 2019; Yu et al., 2014).