Extracellular vesicles shed by follicular lymphoma B cells promote polarization of the bone marrow stromal cell niche

Abstract Follicular lymphoma (FL) originates in the lymph nodes (LNs) and infiltrates bone marrow (BM) early course of disease. BM FL B cells are characterized by a lower cytological grade, decreased proliferation, specific phenotypic subclonal profile. Mesenchymal stromal (MSCs) obtained from display gene expression profile (GEP), including enrichment for lymphoid cell signature, an increased capacity to sustain B-cell growth. However, mechanisms triggering formation medullar permissive niche have not been identified. In current work, we demonstrate that produce extracellular vesicles (EVs) can be internalized BM-MSCs, making them more efficient support survival quiescence. Accordingly, EVs purified plasma activate transforming growth factor ?–dependent independent pathways BM-MSCs modify their GEP, upregulation factors classically associated with hematopoietic stem niche, CXCL12 angiopoietin-1. Moreover, provide first characterization allowing definition landscape molecular interactions they could engage EV-primed BM-MSCs. This work identifies FL-derived as putative mediators stroma polarization supports further investigation clinical interest targeting crosstalk between malignant cells.