IDH2 and acute myeloid leukemia: Modern AML trials should prioritize the biology of therapeutic selection over morphology-driven endpoints, recognizing that actionable resistance—emergent RAS/MAPK clones, secondary FLT3 TKD/gatekeeper alleles (e.g., D835, F691L), and IDH isoform switching—arises before overt relapse and is detectable at MRD or pre-MRD fluctuations (Short et al., 2024).