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<p>Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing participants. Furthermore, signaling analyses suggested active intercellular communication involving a proliferation-inducing ligand and B cell maturation antigen, potentially promoting tumor growth and survival. Lastly, using independent discovery and validation cohorts, we demonstrated that integrating immune cell signatures with known tumor cytogenetics and individual characteristics significantly improves stratification for the prediction of survival.</p>

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A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月9日

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  • William C. Pilcher,
  • Lijun Yao,
  • Edgar Gonzalez-Kozlova,
  • Yered Pita-Juarez,
  • Dimitra Karagkouni,
  • Chaitanya R. Acharya,
  • Marina E. Michaud,
  • Mark Hamilton,
  • Shivani Nanda,
  • Yizhe Song,
  • Kazuhito Sato,
  • Julia T. Wang,
  • Sarthak Satpathy,
  • Yuling Ma,
  • Jessica Schulman,
  • Darwin D’Souza,
  • Reyka G. Jayasinghe,
  • Denis Ohlstrom,
  • Katherine E. Ferguson,
  • Giulia Cheloni,
  • Mojtaba Bakhtiari,
  • Nick Pabustan,
  • Kai Nie,
  • Jennifer A. Foltz,
  • Isabella Saldarriaga,
  • Rania Alaaeldin,
  • Eva Lepisto,
  • Rachel Chen,
  • Mark A. Fiala,
  • Beena E. Thomas,
  • April Cook,
  • Junia Vieira Dos Santos,
  • Chiang I-ling,
  • Igor Figueiredo,
  • Julie Fortier,
  • Michael Slade,
  • Stephen T. Oh,
  • Michael P. Rettig,
  • Emilie Anderson,
  • Ying Li,
  • Surendra Dasari,
  • Michael A. Strausbauch,
  • Vernadette A. Simon,
  • I-ling Chiang,
  • Nikolaos Kalavros,
  • Jennifer Rogers,
  • Travis Dawson,
  • Brian H. Lee,
  • Geoffrey Kelly,
  • Laura Walker,
  • Nicolas F. Fernandez,
  • John Leech,
  • Jarod Morgenroth-Rebin,
  • Krista Angeliadis,
  • Matthew A. Wyczalkowski,
  • Song Cao,
  • Omar Ibrahim,
  • Roderick Lin,
  • Todd A. Fehniger,
  • Andrew Houston,
  • Emir Radkevich,
  • Adeeb H. Rahman,
  • Zhihong Chen,
  • Alessandro Lagana,
  • John F. DiPersio,
  • Jacalyn Rosenblatt,
  • Seunghee Kim-Schulze,
  • Sagar Lonial,
  • Shaji Kumar,
  • Swati S. Bhasin,
  • Taxiarchis Kourelis,
  • Madhav V. Dhodapkar,
  • Ravi Vij,
  • David Avigan,
  • Hearn J. Cho,
  • George Mulligan,
  • Li Ding,
  • Sacha Gnjatic,
  • Ioannis S. Vlachos,
  • Manoj Bhasin

摘要

Multiple myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We developed an Immune Atlas of MM by generating profiles of 1,397,272 single cells from the bone marrow (BM) of 337 newly diagnosed participants and characterized immune and hematopoietic cell populations. Cytogenetic risk-based analysis revealed heterogeneous associations with T cells of BM, with 17p13 deletion showing distinct enrichment of a type 1 interferon signature. The disease progression-based analysis revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing participants. Furthermore, signaling analyses suggested active intercellular communication involving a proliferation-inducing ligand and B cell maturation antigen, potentially promoting tumor growth and survival. Lastly, using independent discovery and validation cohorts, we demonstrated that integrating immune cell signatures with known tumor cytogenetics and individual characteristics significantly improves stratification for the prediction of survival.