TY  - JOUR
AU  - Lutz, Raphael
AU  - Poos, Alexandra
AU  - Solé-Boldo, Llorenç
AU  - John, Lukas
AU  - Wagner, Johanna
AU  - Prokoph, Nina
AU  - Baertsch, Marc A
AU  - Vonficht, Dominik
AU  - Palit, Subarna
AU  - Brobeil, Alexander
AU  - Mechtersheimer, Gunhild
AU  - Hildenbrand, Nina
AU  - Hemmer, Stefan
AU  - Steiger, Simon
AU  - Horn, Sabrina
AU  - Pepke, Wojciech
AU  - Spranz, David M
AU  - Rehnitz, Christoph
AU  - Sant, Pooja
AU  - Mallm, Jan-Philipp
AU  - Friedrich, Mirco J
AU  - Reichert, Philipp
AU  - Huhn, Stefanie
AU  - Trumpp, Andreas
AU  - Rippe, Karsten
AU  - Haghverdi, Laleh
AU  - Fröhling, Stefan
AU  - Müller-Tidow, Carsten
AU  - Hübschmann, Daniel
AU  - Goldschmidt, Hartmut
AU  - Willimsky, Gerald
AU  - Sauer, Sandra
AU  - Raab, Marc S
AU  - Haas, Simon
AU  - Weinhold, Niels
TI  - Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.
JO  - Science immunology
VL  - 10
IS  - 104
SN  - 2470-9468
CY  - Washington, DC
PB  - AAAS
M1  - DKFZ-2025-00315
SP  - eadp6667
PY  - 2025
N1  - #EA:A010#EA:A360#LA:A360#
AB  - 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.
KW  - Multiple Myeloma: immunology
KW  - Multiple Myeloma: pathology
KW  - Humans
KW  - Tumor Microenvironment: immunology
KW  - Bone Marrow: immunology
KW  - Bone Marrow: pathology
LB  - PUB:(DE-HGF)16
C6  - pmid:39919199
DO  - DOI:10.1126/sciimmunol.adp6667
UR  - https://inrepo02.dkfz.de/record/298615
ER  -