The effects of inflammation on healthy and malignant haematopoiesis
Hematopoietic stem cells (HSCs) only function when localised in complex niches within the bone marrow microenvironment, where stroma and haematopoietic cell types cooperate to regulate their function. HSC fate is affected by multiple stresses such as transplantation, infection and leukaemia growth. Over the years we have used intravital microscopy to identify dynamic changes in HSC-niche interactions and stress-induced remodelling of the bone marrow microenvironment. In an experimental model of severe acute infection, we identified multiple factors involved in regulating HSC proliferation and function, and we improved HSC fitness by targeting niche components. Similar to healthy haematopoiesis, malignant haematopoiesis is affected by inflammation. Using a murine model of acute myeloid leukaemia we uncovered a complex relationship between AML stemness, differentiation and immunoevasion, with important implications for the development of successful immunotherapy approaches.
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Imperial College London, UK
Seminar suggested by Giulia CARZEDDA