Role of the haematopoietic stem cell niche in pre-leukaemic clonal haematopoiesis and myelodysplatic syndromes

Haematopoietic stem cells (HSC) sustain the production of blood cells and are located in the bone marrow, where other cell types, known as the niche, support and regulate their function. Mutations of HSCs are associated with myelodysplastic syndromes (MDS) and pre-leukaemic conditions. The mutations have a competitive advantage over healthy HSCs. MDS is characterised by the accumulation of dysfunctional HSCs, inefficient production of blood cells and a higher risk to developing leukaemia. There are currently no effective treatments for MDS. MDS-HSCs are highly dependent on the niche where they reside but it is still largely unknown exactly how.

Targeting the MDS-HSC niche constitutes a novel and unexplored therapeutic avenue. I will identify the niche and the mechanisms by which it confers advantage to MDS-HSCs.

My findings will lead to the design of new therapies for MDS.