Branched evolution of a U2AF1-mutated progenitor to distinct B-lymphoblast and myeloid clones. Truncal mutation: Initially, a U2AF1 mutation is proposed to have arisen in a lineage-uncommitted progenitor. Lineage-specific evolution: Subsequently, separate subclones acquired BCOR and ASXL1 mutations, which appeared lineage restricted. Subclonal evolution within a lineage: Finally, the B-lymphoblast and myeloid clones continued to evolve by acquisition of additional subclonal mutations. Morphologic findings of increased blasts after initial minihyper CVD (lower left, 600× original magnfication) and morphologic dyspoiesis after 2 cycles of inotuzumab are shown. Dysplastic features included megakaryocytes with abnormal lobation (middle image, 600× original magnification) and erythroid multinuclearity, nuclear irregularity, and nuclear fragmentation (right, 2100× total magnification). All microscopic images represent May Grunwald-Giemsa stains.