Evolution and emergence of a dominant JAK2^V617Fand IDH1^R132Cco-mutant clone induced by ivosidenib. Bone marrow morphology with hemoxylin and eosin stain (A), CD34 immunostain (B), Wright-Giemsa stain of bone marrow aspirate (C), and immunophenotype of the leukemic blasts (D) before initiating IDH inhibitor treatment. Bone marrow morphology with hemoxylin and eosin stain (E), CD34 immunostain (F), Wright-Giemsa stain of bone marrow aspirate (G), and immunophenotype of the leukemic blasts (H) following treatment with ivosidenib. (I) Timeline of complete blood count results in relation to therapy: 1, start of ivosidenib; 2 and 3, therapeutic phlebotomy; 4, decitabine/ruxolitinib; and 5, low-dose cytarabine/venetoclax. (J) Clonal architecture analysis using single-cell sequencing. Bar plot (top) depicts the number of cells identified with a given genotype (bottom) ranked by decreasing frequency of the clone. Cell counts for each clone is depicted with error bars derived from random resampling analysis. (K) Droplet digital PCR results on the marrow before IDH inhibitor treatment. (L) Illustration of JAK2, IDH1, and IDH2 mutational exclusivity patterns in AML from cBioportal. ANC, absolute neutrophil count; Hct, hematocrit; PCS, phycoerythrin-Cy5; WBC, white blood cell; WT, wild-type.