Investigating enhanced intracellular stress response in leukemic stem cells as a mechanism of disease persistence in acute myeloid leukemia associated with severe congenital neutropenia

• Applicants: Professor Manfred Claassen, Ph.D.; Professorin Julia Skokowa, Ph.D.
• Subject Area: Hematology, Oncology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536712810

In acute myeloid leukemia (AML), slowly proliferating leukemia stem cells (LSCs) resist conventional therapies evolving over time and causing disease relapse. Here, we aim to investigate the processes of pre-LSCs to LSCs evolution and their persistence in patients with AML associated with severe congenital neutropenia. We will apply advanced in vitro and in vivo experimental models analyses of leukemia development in CN, perform bulk-RNA-seq, scRNA-seq and MACSima analyses, and, ultimately, develop machine learning (ML). algorithms to analyse omics data and identify main pathways that trigger leukemia development in CN. We will focus on the role of integrated stress response in this process. ML-derived hypotheses will be functionally validated. Our ultimate aim is to establish new therapeutic tools that target the leukemogenic pathways associated with integrated stress response in AML.

• DFG Programme: Research Grants