B05: Characterizing lineage plasticity of KMT2A/AFF1-rearranged acute leukemia under therapeutic pressure from CAR T cells

Project B05 will characterize lineage plasticity of KMT2A-rearranged acute leukemia under therapeutic pressure from CAR-T cells. Mechanisms mediating the lymphoid to myeloid lineage switch upon CD19 CAR T cell therapy will be analyzed using primary samples and combined single-cell transcriptomics and clonal tracking. Lineage-switch mechanisms will be further studied in KMT2A/AFF1 leukemia PDX-mouse models, and combination treatments for KMT2A/AFF1 leukemias using hypomethylating agents and CAR-Ts will be developed and optimized.