Thymus-specific B-cell program identified as origin of PMBCL
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Researchers combining single-cell multiomics and spatial profiling across human tissues have identified a thymus-specific B-cell differentiation program that links CCL17+ and germinal-center-like B-cell states. In primary mediastinal B-cell lymphoma (PMBCL), malignant cells share transcriptional and epigenetic features with CCL17+ thymic B cells and occupy early clonal positions in reconstructed B-cell receptor phylogenies, pointing to these cells as a likely origin of the disease. Notably, this CCL17+ state also persists in tumor microenvironments distinct from the thymic niche, supporting the idea that the differentiation program is redeployed during thymic B-cell lymphomagenesis rather than simply retained in place. The findings, posted as a preprint in Cancer Biology, provide a developmental framework for PMBCL; validation in independent cohorts and functional studies of the program remain open questions.
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- bioRxivPickDevelopmental origins of thymic B-cell lymphomas
Integrating single-cell multiomics and spatial analysis across human tissues, researchers identified a thymus-specific B-cell differentiation program linking CCL17⁺ and germinal center-like B-cell states. Malignant cell states in PMBCL share transcriptional and epigenetic features with CCL17⁺ thymic B cells and occupy early clonal positions in reconstructed BCR phylogenies. This state also persists in tumor microenvironments distinct from the thymic niche, supporting redeployment of the program during thymic B-cell lymphomagenesis.
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