The role of molecular profiling in AML diagnosis, therapeutic selection, and disease monitoring. In this schematic, AML development is depicted as the terminal stage in a phenotypic continuum from prior clonal hematopoiesis and myelodysplasia. A sample of acquired mutations (not all encompassing) driving disease progression is listed with respect to time (x-axis), in addition to a model for longitudinal molecular assessment. Relative clonal size is depicted on the y-axis. In this sample case, mutational profiling at diagnosis aids in selection of a therapy that leads to a significant reduction of leukemic burden and establishment of a first complete remission (CR). From here, 3 possible scenarios are depicted: sustained remission with expansion of preexisting nonmalignant clones (clonal hematopoiesis of indeterminate potential [CHIP],^13-17  disease relapse with development and outgrowth of a leukemic subclone (blue),⁵¹  and control of persistent disease with targeted agents leading to cellular differentiation without killing (eg, IDH1/2 inhibitors, hypomethylating agents).⁴  IDH, isocitrate dehydrogenase; MRD, minimal residual disease.