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

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Item Type:	Article
Title:	Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma
Creators Name:	Lutz, R., Poos, A.M., Solé-Boldo, L., John, L., Wagner, J., Prokoph, N., Baertsch, M.A., Vonficht, D., Palit, S., Brobeil, A., Mechtersheimer, G., Hildenbrand, N., Hemmer, S., Steiger, S., Horn, S., Pepke, W., Spranz, D.M., Rehnitz, C., Sant, P., Mallm, J.P., Friedrich, M.J., Reichert, P., Huhn, S., Trumpp, A., Rippe, K., Haghverdi, L., Fröhling, S., Müller-Tidow, C., Hübschmann, D., Goldschmidt, H., Willimsky, G., Sauer, S., Raab, M.S., Haas, S. and Weinhold, N.
Abstract:	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.
Keywords:	Bone Marrow, Multiple Myeloma, Tumor Microenvironment
Source:	Science Immunology
ISSN:	2470-9468
Publisher:	American Association for the Advancement of Science
Volume:	10
Number:	104
Page Range:	eadp6667
Date:	February 2025
Official Publication:	https://doi.org/10.1126/sciimmunol.adp6667
PubMed:	View item in PubMed

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