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Role of the haematopoietic stem cell niche in pre-leukemic clonal haematopoiesis and myelodysplatic syndromes (360G-Wellcome-210424_Z_18_Z)

Myelodysplastic syndromes (MDS) are prototype pre-leukemic conditions that initiate in haematopoietic stem cells (HSC). These are characterized by clonal HSC expansion, inefficient production of mature blood cells and a higher propensity to progress to acute myelogenous leukaemia. Multiple studies suggest that MDS-HSCs are highly dependent on the bone marrow niche. It is possible that leukemic stem cells exploit the normal remodelling capacity of the niche to create a self-reinforcing leukemic environment, thereby favouring leukaemia development. However the molecular mechanisms involved in this process are still largely unknown. This project aims at identifying the signalling networks involved in the bidirectional crosstalk between MDS-HSCs and specific niche cells, and how this contributes to MDS pathogenesis in both mouse and human. A multidisciplinary approach will be used, combining transcriptomic analysis of niche cells and HSCs, 3D-imaging of the bone marrow and computational modelling. I will investigate which essential interactions between MDS-HSCs and their niches are responsible for their competitive advantage over normal HSCs. These studies have the goal of ultimately disrupting these interactions as a novel therapeutic avenue for MDS, a disease that currently has very few treatment options.

£1,374,297

21 Feb 2018

Grant details
Amount Awarded 1374297
Applicant Surname Cunha Luis
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2018-02-21T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 210424/Z/18/Z
Lead Applicant Dr Tiago Cunha Luis
Planned Dates: End Date 2023-11-01T00:00:00+00:00
Planned Dates: Start Date 2018-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Anne Dell
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