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

• Subject Area: Hematology, Oncology ; Immunology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533056198

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1709: Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Heads: Dr. Andrea Schmidts; Dr. Maria-Luisa Schubert