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Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain...

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Main Authors: Lutz, Raphael (Author) , Poos, Alexandra (Author) , Solé-Boldo, Llorenç (Author) , John, Lukas (Author) , Wagner, Johanna (Author) , Prokoph, Nina (Author) , Bärtsch, Marc-Andrea (Author) , Vonficht, Dominik (Author) , Palit, Subarna (Author) , Brobeil, Alexander (Author) , Mechtersheimer, Gunhild (Author) , Hildenbrand, Nina Marie (Author) , Hemmer, Stefan (Author) , Steiger, Simon (Author) , Horn, Sabrina (Author) , Pepke, Wojciech (Author) , Spranz, David Maximilian (Author) , Rehnitz, Christoph (Author) , Sant, Pooja (Author) , Mallm, Jan-Philipp (Author) , Friedrich, Mirco (Author) , Reichert, Philipp (Author) , Huhn, Stefanie (Author) , Trumpp, Andreas (Author) , Rippe, Karsten (Author) , Haghverdi, Laleh (Author) , Fröhling, Stefan (Author) , Müller-Tidow, Carsten (Author) , Hübschmann, Daniel (Author) , Goldschmidt, Hartmut (Author) , Willimsky, Gerald (Author) , Sauer, Sandra (Author) , Raab, Marc-Steffen (Author) , Haas, Simon (Author) , Weinhold, Niels (Author)
Format: Article (Journal)
Language:English
Published: February 28, 2025
In: Science immunology
Year: 2025, Volume: 10, Issue: 104, Pages: 1-16
ISSN:2470-9468
DOI:10.1126/sciimmunol.adp6667
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciimmunol.adp6667
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/sciimmunol.adp6667
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Author Notes:Raphael Lutz, Alexandra M. Poos, Llorenç Solé-Boldo, Lukas John, Johanna Wagner, Nina Prokoph, Marc A. Baertsch, Dominik Vonficht, Subarna Palit, Alexander Brobeil, Gunhild Mechtersheimer, Nina Hildenbrand, Stefan Hemmer, Simon Steiger, Sabrina Horn, Wojciech Pepke, David M. Spranz, Christoph Rehnitz, Pooja Sant, Jan-Philipp Mallm, Mirco J. Friedrich, Philipp Reichert, Stefanie Huhn, Andreas Trumpp, Karsten Rippe, Laleh Haghverdi, Stefan Fröhling, Carsten Müller-Tidow, Daniel Hübschmann, Hartmut Goldschmidt, Gerald Willimsky, Sandra Sauer, Marc S. Raab, Simon Haas, Niels Weinhold
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Summary:The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow-confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.
Item Description:Veröffentlicht: 7. Februar 2025
Gesehen am 05.08.2025
Physical Description:Online Resource
ISSN:2470-9468
DOI:10.1126/sciimmunol.adp6667

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