Lymphoma B cells remodel bone marrow stromal cell network into extracellular matrix-producing cancer-associated fibroblasts (bulk rnaseq)

Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma. Overall design: The DOHH2 cells harboring the mention D19 or D40 in the sample name were sorted using flow cytometry associated cell sorting, from DOHH2 grafted RAG?c femurs. The number indicates the day post-graft when we sorted the DOHH2 cells. The "D0" samples represent a sample of cultured DOHH2 from the day of the graft (to compare the cells that were injected before and after in-vivo growth.