Mesenchymal COX2-PG secretome engages NR4A-WNT signalling axis in haematopoietic progenitors to suppress anti-leukaemia immunity.

ABSTRACT: The bone marrow (BM) microenvironment (niche) plays important roles in supporting normal/abnormal haematopoiesis. We investigated the interaction between leukaemic mesenchymal niche and haematopoietic stem and progenitor cells (HSPCs) using the model of Fanconi anaemia (FA), a genetic disorder characterized by BM failure and leukaemia. Healthy donor HSPCs co-cultured on mesenchymal stromal cells (MSCs) derived from FA patients with acute myeloid leukaemia (AML) exhibited higher human engraftment and myeloid expansion in Non-obese diabetic severe combined immunodeficiency IL-2γ^-/- /SGM3 recipients. Untargeted metabolomics analysis revealed the progressively elevated prostaglandins (PGs) in the MSCs of FA patients with myelodysplastic syndromes (MDS) and AML. Reduced secretion of

SUBMITTER: Wu L 

PROVIDER: S-EPMC6391996 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature