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@ARTICLE{Lutz:298615,
      author       = {R. Lutz$^*$ and A. Poos$^*$ and L. Solé-Boldo and L.
                      John$^*$ and J. Wagner$^*$ and N. Prokoph$^*$ and M. A.
                      Baertsch$^*$ and D. Vonficht$^*$ and S. Palit and A. Brobeil
                      and G. Mechtersheimer and N. Hildenbrand and S. Hemmer and
                      S. Steiger$^*$ and S. Horn and W. Pepke and D. M. Spranz and
                      C. Rehnitz and P. Sant$^*$ and J.-P. Mallm$^*$ and M. J.
                      Friedrich and P. Reichert and S. Huhn and A. Trumpp$^*$ and
                      K. Rippe$^*$ and L. Haghverdi and S. Fröhling$^*$ and C.
                      Müller-Tidow and D. Hübschmann$^*$ and H. Goldschmidt and
                      G. Willimsky$^*$ and S. Sauer and M. S. Raab$^*$ and S.
                      Haas$^*$ and N. Weinhold$^*$},
      title        = {{B}one marrow breakout lesions act as key sites for
                      tumor-immune cell diversification in multiple myeloma.},
      journal      = {Science immunology},
      volume       = {10},
      number       = {104},
      issn         = {2470-9468},
      address      = {Washington, DC},
      publisher    = {AAAS},
      reportid     = {DKFZ-2025-00315},
      pages        = {eadp6667},
      year         = {2025},
      note         = {#EA:A010#EA:A360#LA:A360#},
      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     = {Multiple Myeloma: immunology / Multiple Myeloma: pathology
                      / Humans / Tumor Microenvironment: immunology / Bone Marrow:
                      immunology / Bone Marrow: pathology},
      cin          = {A010 / A360 / B340 / B066 / W192 / HD01 / BE01 / W015},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)A360-20160331 /
                      I:(DE-He78)B340-20160331 / I:(DE-He78)B066-20160331 /
                      I:(DE-He78)W192-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)BE01-20160331 / I:(DE-He78)W015-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39919199},
      doi          = {10.1126/sciimmunol.adp6667},
      url          = {https://inrepo02.dkfz.de/record/298615},
}