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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.<\/jats:p>","DOI":"10.1126\/sciimmunol.adp6667","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T13:59:46Z","timestamp":1738936786000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":27,"title":["Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6214-308X","authenticated-orcid":true,"given":"Raphael","family":"Lutz","sequence":"first","affiliation":[{"name":"Heidelberg Myeloma Center, Department of Internal Medicine V, Heidelberg University Hospital, Medical Faculty, Heidelberg University, Heidelberg, Germany."},{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine 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