A trio of BCL2 variants identified upon venetoclax and azacitidine progression. (A) Fish plot representation showing changes in clonal architecture over time (x-axis), with bone marrow blasts (%) and treatments administered shown. Variants were characterized using a clinical NGS panel and relapse clonal architecture from single-cell DNA sequence.14 (B-D) Multiomic single-cell characterization of bone marrow from day 487 (panel A). (B) Two-dimensional UMAP plot showing specific phenotypic populations based on antibody tags (right). Mononuclear cells clustered into 4 main blood cell compartments including AML blast cells (red). Identified DNA clones (blue, orange, and green) are overlaid onto phenotypic populations (left). (C) The proportion of cells either wild-type (WT) or heterozygote for indicated GATA2 and BCL2 variants. (D) Proportion of each mutant clone within specified blood cell lineages. AZA, azacitidine; CLAG, cladribine, cytarabine, granulocyte colony-stimulating factor; CR, complete remission; HD, high-dose; HET, heterozygous; HOM, homozygous; mido, midostaurin; UMAP, Uniform Manifold Approximation and Projection; VEN, venetoclax; 7 + 3, cytarabine/daunorubicin.
