Clinical course for a patient with AML who is refractory or eventually relapses. (A) Patients with AML present with high leukemia blast burden (brown), receive induction chemotherapy, and often enter complete remission. Some patients have refractory disease, and most patients who achieve complete remission ultimately relapse. Patients who are refractory to induction therapies never clear their disease, as assessed by morphology. Those who enter complete remission often have persistent measurable residual disease (MRD), below levels detectable by morphologic analysis. These patients relapse, with variable clonal dynamics, but often have an expanded LSC (red) compartment. Those who relapse late may have had persistent pHSCs (purple) that reevolved into AML. (B) MRD can be assessed by morphology using microscopy (detection limit, 10−2 cells), cytogenetics (10−2 cells), multiparameter flow cytometry (10−4 cells), or mutation-specific polymerase chain reaction (PCR) or next-generation sequencing (NGS; 10−6 cells). FISH, fluorescence in situ hybridization; FITC, fluorescein isothiocyanate; PE, phycoerythrin.
