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Spatial profiling identifies a distinct and topographically-defined tumor microenvironment that emerges during multiple myeloma evolution

Marnix Koops, Luca Bertamini, Natalie Papazian, Charlotte Korst, Mátyás János. Budai, Remco M. Hoogenboezem, Mathijs A. Sanders, Bronno van der Holt, Mark van Duin, Annemiek Broijl, Péter Balogh, Sonja Zweegman, Marc HGP. Raaijmakers, Niels W.C.J. van de Donk, Zoltán Kellermayer, Pieter Sonneveld, Tom Cupedo

Blood Cancer Discovery · 2026

Vollständiger Abstract

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Abstract The pathobiology of multiple myeloma is influenced by cells of the bone marrow, but whether tumor support is organized in a spatially-defined tumor microenvironment (TME) remains unclear. Using spatial transcriptomics and imaging mass cytometry, we show that myeloma cells initially exist as scattered cells throughout the marrow, yet with disease evolution condense into a spatially-defined TME. Dense tumor nodules contain a cellular ecosystem distinct from the surrounding marrow, enriched for macrophages, conventional dendritic cells, and CD8⁺ T cells, as well as endothelial cells and THY1⁺ mesenchymal stromal cells. Conversely, neutrophil lineage cells are absent from this TME but interact with scattered myeloma cells outside of dense nodules. Presence of the dense tumor architecture at diagnosis confers a worse prognosis, emphasizing the relevance of spatial organization of the bone marrow. Together, these findings define a discrete spatial and cellular myeloma TME, that provides spatially-guided insights into patient stratification and disease pathobiology.

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Autor:innen
Marnix Koops, Luca Bertamini, Natalie Papazian, Charlotte Korst, Mátyás János. Budai, Remco M. Hoogenboezem, Mathijs A. Sanders, Bronno van der Holt, Mark van Duin, Annemiek Broijl, Péter Balogh, Sonja Zweegman, Marc HGP. Raaijmakers, Niels W.C.J. van de Donk, Zoltán Kellermayer, Pieter Sonneveld, Tom Cupedo
Quelle
Blood Cancer Discovery
Publikation
2026-01-01
Band / Ausgabe
Nicht angegeben
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ISSN / ISBN
2643-3230, 2643-3249
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Marnix Koops, Luca Bertamini, Natalie Papazian, Charlotte Korst, Mátyás János. Budai, Remco M. Hoogenboezem, Mathijs A. Sanders, Bronno van der Holt, Mark van Duin, Annemiek Broijl, Péter Balogh, Sonja Zweegman, Marc HGP. Raaijmakers, Niels W.C.J. van de Donk, Zoltán Kellermayer, Pieter Sonneveld, Tom Cupedo (2026). Spatial profiling identifies a distinct and topographically-defined tumor microenvironment that emerges during multiple myeloma evolution. Blood Cancer Discovery. https://doi.org/10.1158/2643-3230.bcd-26-0080
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