Interrogating Clonal Evolution in Acute Leukemias through Single-Cell Multi-omic (DNA+Fusion and DNA+Immunophenotype) Analysis

In this webinar, Morgan Drucker, MD, Pediatric Hematology/Oncology Fellow at Cincinnati Children's Hospital Medical Center, presents findings from datasets generated by her team at Cincinnati Children's Hospital using single-cell multi-omics. She discusses two distinct patient cohorts: adults with NPM1-mutated AML and pediatric patients with KMT2A-rearranged acute leukemias, whose underlying genetic changes (NPM1 mutations and KMT2A rearrangements) both rely on interactions between the protein menin and KMT2A.

For the NPM1-mutant AML cohort, her team performed simultaneous single-cell molecular profiling and cell surface protein expression using an expanded panel of antibody targets, through which they uncovered unique genotype-immunophenotype correlations across different disease states. In the KMT2A-rearranged cohort, the team performed optimization of a novel custom multi-omic amplicon panel to simultaneously detect KMT2A-fusion products, somatic co-mutations, and targeted gene expression. Single-cell analysis revealed unique fusion and genotype-specific alterations in clonal architecture and target gene expression.