The expansion of nonleukemic hematopoietic clonal populations is frequently observed following induction therapy for de novo AML patients. Somatic mutations were identified at the time of diagnosis, after induction chemotherapy, and at long-term follow-up using enhanced exome sequencing. Mutations present in the AML founding clone or subclone(s) are highlighted in red. Mutations present in rising clones are highlighted in blue. (A) Representative data from a patient with no evidence of clonal hematopoiesis after cytoreductive therapy. (B) Representative data from a patient with recurrence of his AML after chemotherapy with the concomitant expansion of an AML subclone harboring additional somatic mutations (shown in green). (C-G) All 5 patients with validated genetic evidence showing expansion of a nonleukemic hematopoietic clone after chemotherapy. (H) Proposed model of clonal evolution under the influence of cytoreductive chemotherapy in UPN 192545. (I) Sorting strategy used to isolate relapsed CD34⁺CD45^dimSSC^low leukemic blasts in UPN 746628. (J) ddPCR plot assessing the presence of the TP53 e4-1 allele in the leukemic blast population of UPN 746628. Droplets containing only the TP53 e4-1 allele are highlighted in orange. droplets containing the wild-type allele (with or without the TP53 e4-1 allele) are highlighted in blue, and empty droplets are gray. The number of droplets in each gate is indicated. A.U., arbitrary units.