PIXEL Profiling and functional analysis of the Immune environment of eXtramedullary leukemia rELapses

Acute myeloid leukemia (AML) is an aggressive malignancy of the hematopoietic system and mainly affects the bone marrow and blood. Blood stem cell transplantation (SCT) is a potentially curative approach for this aggressive disease. Unfortunately, a significant subset of patients relapses after SCT, making this situation one of the primary targets of AML research with a tremendous potential to increase survival if overcome. Interestingly, leukemia relapse after transplantation frequently occurs outside the bone marrow and/or blood. Any body tissue can be affected in these cases, causing a complication called extramedullary leukemia (EML). It is essential to decipher the mechanisms behind this AML formation in non-bone marrow sites. This knowledge might result in novel therapeutic approaches targeting this fatal complication after transplantation. This project will screen for molecular aberrations affecting a specific cell regulatory network in EML specimens. We will focus on samples from patients where EML occurred after transplantation. Therefore, we will interact with the other partners from this international consortium and analyze data, where the complete genomic information of the cell is investigated. We will then use these data to delineate the role of detected aberrations in functional EML models. In more detail, these models employ leukemia cells and test their potential to invade tissues in a laboratory setting. We will genetically modify these cells and create the lesions detected in the patient samples. By comparing the genetically modified cells to the unmodified controls, we can delineate whether specific genetic abnormalities play a role in the development of EML after transplantation. Ultimately, this creates a link to other partners within this consortium, who will use this information to develop novel therapeutic approaches.