In a new study, researchers identified extracellular vesicles (EVs) as a means by which follicular lymphoma (FL) B cells appear to affect bone marrow (BM) stroma polarization. The study results were reported in the journal Blood.
Infiltration of the BM is common in cases of FL, but, as the researchers explained in their report, the characteristics of FL B cells within the BM often differ from those in the lymph nodes. FL B cells begin in the lymph nodes before migration to the BM where mutations develop that are specific to the BM, according to the researchers. There is also evidence of crosstalk between tumor B cells and the BM microenvironment, and although EVs have been found in association with cancer cells in other hematologic malignancies, their role and features in FL have been unclear.
The researchers conducting this study were based at institutions across France. The research team obtained aspirates from lymph nodes and BM of patients upon diagnosis of FL, and they additionally collected BM aspirates from other age-matched patients. Gene expression profiling was conducted on BM mesenchymal stromal cells (MSCs) and on lymphoid stromal cells (LSCs) obtained from lymph nodes. Other analyses were also performed, such as an interactome analysis to analyze interactions between FL B cells and stromal cells.
FL B cell-associated EVs were identified and characterized, and these vesicles ranged from 60nm to 300 nm in size, with a mode of 90nm to 110nm. The concentration of EVs ranged from 4×108 to 2.3×1010 particles/104 malignant B cells. In experiments in which FL B cells were cocultured with BM MSCs derived from healthy donors, the MSCs appeared to support survival of the FL B cells, as demonstrated by a reduction in the percentage of apoptotic FL B cells. When FL-derived EVs were applied in this system, this effect was further enhanced (P <.01).
Additionally, gene expression profiling of BM MSCs from healthy donors showed changes upon treatment with FL-derived EVs. FL-associated BM MSCs and lymph node LSCs showed distinct signatures of upregulated genes, but FL-associated BM MSCs also showed enrichment of a signature linked to EVs. In further analyses, when healthy donor BM MSCs were treated with FL-derived EVs, the healthy donor MSCs appeared to demonstrate a phenotype resembling that of FL-infiltrating stromal cells and the hematopoietic stem cell (HSC) stromal niche. This included expression of specific transcription factors, cytokines, and chemokines previously linked to HSC stromal cell niches, such as CXCL12, which the researchers explained supports the migration, adhesion, and survival of FL B cells.
“Our study suggests that FL-derived EVs should be considered as putative mediators of BM stroma polarization,” the researchers concluded in their report. They also explained that whether EVs play a role in FL pathogenesis is a topic awaiting further clarification.
Dumontet E, Pangualt C, Roulois D, et al. Extracellular vesicles shed by follicular lymphoma B cells promote polarization of the bone marrow stromal cell niche. Blood. 2021;138(1):57-70. doi:10.1182/blood.2020008791