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Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level

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Item Type:Article
Title:Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level
Creators Name:John, L. and Poos, A.M. and Brobeil, A. and Schinke, C. and Huhn, S. and Prokoph, N. and Lutz, R. and Wagner, B. and Zangari, M. and Tirier, S.M. and Mallm, J.P. and Schumacher, S. and Vonficht, D. and Solé-Boldo, L. and Quick, S. and Steiger, S. and Przybilla, M.J. and Bauer, K. and Baumann, A. and Hemmer, S. and Rehnitz, C. and Lückerath, C. and Sachpekidis, C. and Mechtersheimer, G. and Haberkorn, U. and Dimitrakopoulou-Strauss, A. and Reichert, P. and Barlogie, B. and Müller-Tidow, C. and Goldschmidt, H. and Hillengass, J. and Rasche, L. and Haas, S.F. and van Rhee, F. and Rippe, K. and Raab, M.S. and Sauer, S. and Weinhold, N.
Abstract:In multiple myeloma spatial differences in the subclonal architecture, molecular signatures and composition of the microenvironment remain poorly characterized. To address this shortcoming, we perform multi-region sequencing on paired random bone marrow and focal lesion samples from 17 newly diagnosed patients. Using single-cell RNA- and ATAC-seq we find a median of 6 tumor subclones per patient and unique subclones in focal lesions. Genetically identical subclones display different levels of spatial transcriptional plasticity, including nearly identical profiles and pronounced heterogeneity at different sites, which can include differential expression of immunotherapy targets, such as CD20 and CD38. Macrophages are significantly depleted in the microenvironment of focal lesions. We observe proportional changes in the T-cell repertoire but no site-specific expansion of T-cell clones in intramedullary lesions. In conclusion, our results demonstrate the relevance of considering spatial heterogeneity in multiple myeloma with potential implications for models of cell-cell interactions and disease progression.
Keywords:Cell Communication, Chromatin Immunoprecipitation Sequencing, Clone Cells, Disease Progression, Multiple Myeloma, Tumor Microenvironment
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5011
Date:17 August 2023
Official Publication:https://doi.org/10.1038/s41467-023-40584-4
PubMed:View item in PubMed

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