Two mechanistic studies chart distinct molecular drivers that enable acute myeloid leukemia (AML) cells to evade cell death and sustain aggressive disease. One report identifies THRAP3 as a promoter of ferroptosis resistance via alternative splicing of SLU7, which stabilizes lipid metabolism and prevents iron-dependent cell death. The second study shows the noncoding RNA RPPH1 activates NF-κB signaling and skews T-cell responses toward Th17, promoting high-risk AML phenotypes. Ferroptosis is an iron-catalyzed form of regulated cell death; these findings nominate splicing modulators, ferroptosis sensitizers, and NF-κB/immune axis interventions as candidate strategies to overcome resistance in high-risk AML.