Identification of the cellular and molecular bone marrow niche of relapse-initiating drug tolerant acute myeloid leukaemia cells

• Applicant: Privatdozent Dr. Linus Angenendt
• Subject Area: Hematology, Oncology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 470563736

Relapse is a major cause of death of patients with AML and the recommendation for allogeneic haematopoietic stem cell transplantation as the most intensive treatment option in first complete remission is based on the individual risk of relapse. Relapse of AML has been considered to be caused by quiescent leukaemic stem cells (LSC) that survive chemotherapy. The LSCs have been proposed to hijack and modify haematopoietic stem cells niches in the bone marrow, that contribute to quiescence and chemotherapy resistance. However, more recently, it has been shown that chemotherapy depletes both, the leukaemic bulk and LSCs. Furthermore, the residual cells after chemotherapy, that initiate relapse, termed leukaemic regenerating cells (LRC), are not enriched for LSCs or quiescent cells in vivo. However, it has not been comprehensively analysed whether these LRCs reside in specialized niches that offer them protection from chemotherapy. In this research project, we plan to identify relevant AML LRC microenvironment components in the bone marrow by a combination of single-cell analyses and multiplexed imaging cytometry with subcellular resolution and single-molecule sensitivity. With this approach, we aim to identify relevant niche cell types, molecules and interaction pathways that contribute to chemotherapy resistance of AML cells. We expect the identification of such interaction pathways to ultimately open up new avenues for therapeutic approaches.

• DFG Programme: WBP Fellowship
• International Connection: Switzerland
• Host: Professor Timm Schroeder, Ph.D.