Host autophagy contribution to hematopoiesis regulation in normal and pathological conditions

Laura Poillet

Under physiological condition, steady-state hematopoiesis is supported by the BM niche, mostly through cytokines/chemokines secretion. Upon cytotoxic treatment or in pathological conditions, changes in the BM niche are observed leading to hematopoietic stem cell (HSCs) deregulation and stress-induced hematopoiesis. This altered BM niche and deregulated hematopoiesis could then be responsible for hematological malignancies, such as leukemia and myelodysplastic syndrome.
We demonstrated that host autophagy, especially bone marrow (BM) niche autophagy, is involved in AML progression and therapeutic resistance.
Using a combination of recently generated genetically engineered mouse models (immunocompetent and immunodeficient) of whole body autophagy deficiency (UbcreERT2/+;Atg7flox/flox) and advanced co-culture systems, our goal is to assess the contribution of host autophagy in steady-state as well as in pathological hematopoiesis and to identify the underlying molecular mechanisms.