TY - JOUR
T1 - Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level
AU - John, Lukas
AU - Poos, Alexandra M.
AU - Brobeil, Alexander
AU - Schinke, Carolina
AU - Huhn, Stefanie
AU - Prokoph, Nina
AU - Lutz, Raphael
AU - Wagner, Barbara
AU - Zangari, Maurizio
AU - Tirier, Stephan M.
AU - Mallm, Jan Philipp
AU - Schumacher, Sabrina
AU - Vonficht, Dominik
AU - Solé-Boldo, Llorenç
AU - Quick, Sabine
AU - Steiger, Simon
AU - Przybilla, Moritz J.
AU - Bauer, Katharina
AU - Baumann, Anja
AU - Hemmer, Stefan
AU - Rehnitz, Christoph
AU - Lückerath, Christian
AU - Sachpekidis, Christos
AU - Mechtersheimer, Gunhild
AU - Haberkorn, Uwe
AU - Dimitrakopoulou-Strauss, Antonia
AU - Reichert, Philipp
AU - Barlogie, Bart
AU - Müller-Tidow, Carsten
AU - Goldschmidt, Hartmut
AU - Hillengass, Jens
AU - Rasche, Leo
AU - Haas, Simon F.
AU - van Rhee, Frits
AU - Rippe, Karsten
AU - Raab, Marc S.
AU - Sauer, Sandra
AU - Weinhold, Niels
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85168290227
U2 - 10.1038/s41467-023-40584-4
DO - 10.1038/s41467-023-40584-4
M3 - Article
C2 - 37591845
AN - SCOPUS:85168290227
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5011
ER -