Counteracting NRAS- and c-KIT-driven immune escape in AML by kinase inhibition and T-cell reprogramming (P01)

• Subject Area: Hematology, Oncology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441891347

In the project we plan to investigate whether inhibition of oncogenic signaling in c-KIT-D816V- and NRAS-G12D-driven AML models can induce T-cell reprogramming by reducing immunosuppressive CD155, Gal-9 and adenosine. Aim 2 is dedicated to the discovery of signaling events and transcription factors downstream of c-KIT-D816V and NRAS-G12D that cause CD155, Gal-9 and CD73 expression, whereas MHC-II expression is reduced. In Aim 3 we will validate the findings from mouse models in human AML cells that carry c-KIT-D816V, NRAS-G12D using scRNA-seq, proteomics and metabolomics approaches.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1479: Oncogene-driven immune escape (OncoEscape)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Dr. Franziska Blaeschke, Ph.D., since 1/2026; Professor Dr. Robert Zeiser