Spatial profiling identifies a distinct and topographically-defined tumor microenvironment that emerges during multiple myeloma evolution
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.
Authors
- Pieter Sonneveld (ORCID: https://orcid.org/0000-0002-0808-2237)
- Bronno van der Holt (ORCID: https://orcid.org/0000-0001-6414-2671)
- Zoltán Kellermayer (ORCID: https://orcid.org/0000-0001-9560-6424)
- Remco M. Hoogenboezem (ORCID: https://orcid.org/0000-0002-1719-6455)
- Niels W.C.J. van de Donk (ORCID: https://orcid.org/0000-0002-7445-2603)
- Natalie Papazian (ORCID: https://orcid.org/0000-0002-8616-5652)
- Marnix Koops
- Charlotte L.B.M. Korst (ORCID: https://orcid.org/0009-0005-0191-4343)
- Annemiek Broijl (ORCID: https://orcid.org/0000-0002-0554-8003)
- Tom Cupedo (ORCID: https://orcid.org/0000-0003-1095-4273)
- Mathijs A. Sanders (ORCID: https://orcid.org/0000-0002-8575-9213)
- Marc H.G.P. Raaijmakers (ORCID: https://orcid.org/0000-0002-8315-9417)
- Luca Bertamini (ORCID: https://orcid.org/0000-0003-3722-9696)
- Sonja Zweegman (ORCID: https://orcid.org/0000-0002-5011-1820)
- Péter Balogh (ORCID: https://orcid.org/0000-0001-5749-4775)
- Mark van Duin (ORCID: https://orcid.org/0000-0002-6648-8171)
- Mátyás János. Budai (ORCID: https://orcid.org/0009-0005-3520-1405)
Institutions
- Erasmus MC Cancer Institute (NL)
- Amsterdam University Medical Centers (NL)
- University of Pecs (HU)
- Vrije Universiteit Amsterdam (NL)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-09-01
- DOI
- https://doi.org/10.1158/2643-3230.bcd-26-0080
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00