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

Autor: John L; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Poos AM; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Brobeil A; Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Schinke C; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Huhn S; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany., Prokoph N; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Lutz R; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Wagner B; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany., Zangari M; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Tirier SM; Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Mallm JP; Single Cell Open Lab, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Schumacher S; Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Vonficht D; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Solé-Boldo L; Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany., Quick S; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany., Steiger S; Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Przybilla MJ; Division Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK., Bauer K; Single Cell Open Lab, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Baumann A; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Hemmer S; Department of Orthopedic Surgery, Heidelberg University Hospital, Heidelberg, Germany., Rehnitz C; Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany., Lückerath C; Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany., Sachpekidis C; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany., Mechtersheimer G; Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Haberkorn U; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Dimitrakopoulou-Strauss A; Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany., Reichert P; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany., Barlogie B; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Müller-Tidow C; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany., Goldschmidt H; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany., Hillengass J; Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Rasche L; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA.; Department of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.; Mildred Scheel Early Career Center (MSNZ), University Hospital of Würzburg, Würzburg, Germany., Haas SF; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.; Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany., van Rhee F; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Rippe K; Division of Chromatin Networks, German Cancer Research Center (DKFZ) and BioQuant, Heidelberg, Germany., Raab MS; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sauer S; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany., Weinhold N; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany. niels.weinhold@med.uni-heidelberg.de.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. niels.weinhold@med.uni-heidelberg.de.; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA. niels.weinhold@med.uni-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Aug 17; Vol. 14 (1), pp. 5011. Date of Electronic Publication: 2023 Aug 17.
DOI: 10.1038/s41467-023-40584-4
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: