Rather than treating the niche as passive, regimen engineering can weaponize transient niche disruption to expose blasts and LSCs to cytotoxics and apoptosis-priming backbones, while raising innate-immune set-points to overcome immune evasion, particularly in genomically challenging contexts like TP53-mutant AML (Dong and Konopleva, 2025). Here, TP53 is linked to acute myeloid leukemia.