“Therapeutic targeting of stem cells and their niches in myeloid malignancies”

Our research group “Stem Cells, Ageing and Cancer” aims at providing insights into mechanisms of hematopoietic stem cell malignant transformation, including interactions of this cell with its surrounding microenvironment, and a focus on inflammation, signaling oncometabolites and various cellular components of the stem cell niche. Our goal is the identification of novel therapeutic targets of potential clinical interest for myeloid malignancies.

We will give an overview of our research and present unpublished observations accepted in principle in Nature Communications, where we have uncovered an important role for the metabolite succinate and its membrane receptor Succinate receptor (Sucnr1) in the regulation of hematopoiesis in health and malignancy. Our work suggests that Sucnr1 signaling restricts hematopoiesis at least partially via the hematopoietic stem and progenitor cell compartment and control of S100a9. The dysregulation of Sucnr1 emerges as contributor to malignancy, accounting for SUCNR1 expression as a predictor of prognosis in acute myeloid leukemia (AML) patients and opening new potential therapeutic avenues for these patients.