A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma
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.
Authors
- Michael Slade (ORCID: https://orcid.org/0000-0001-8092-6644)
- Mojtaba Bakhtiari (ORCID: https://orcid.org/0009-0007-6733-0070)
- Michael Strausbauch
- Dimitra Karagkouni (ORCID: https://orcid.org/0009-0007-3961-3399)
- R Chen
- B. Lee
- Omar Ibrahim (ORCID: https://orcid.org/0000-0001-7095-182X)
- T. Kourelis
- Chaitanya R. Acharya (ORCID: https://orcid.org/0000-0001-7149-1749)
- Shivani Nanda (ORCID: https://orcid.org/0000-0001-6358-2392)
- Julie M. Fortier (ORCID: https://orcid.org/0000-0002-5613-9162)
- Denis Ohlstrom (ORCID: https://orcid.org/0000-0003-1920-6319)
- H. J. Cho
- T. Fehniger
- Yuling Ma (ORCID: https://orcid.org/0000-0003-3942-4671)
- Eva M. Lepisto
- Kazuhito Sato (ORCID: https://orcid.org/0000-0003-0589-7454)
- M. Fiala
- Jacalyn Rosenblatt (ORCID: https://orcid.org/0000-0001-5582-8161)
- Rania Alaaeldin (ORCID: https://orcid.org/0000-0002-1084-7323)
- Jessica Schulman (ORCID: https://orcid.org/0000-0002-0131-3485)
- Jennifer A. Foltz (ORCID: https://orcid.org/0000-0001-9158-3464)
- Sarthak Satpathy (ORCID: https://orcid.org/0000-0002-8275-5989)
- J. DiPersio
- Avigan De
- Travis Dawson (ORCID: https://orcid.org/0000-0002-9609-793X)
- Giulia Cheloni (ORCID: https://orcid.org/0000-0002-7682-3826)
- Katherine Ferguson (ORCID: https://orcid.org/0009-0000-0988-2378)
- Andrew Houston (ORCID: https://orcid.org/0000-0002-3837-4695)
- Alessandro Laganà (ORCID: https://orcid.org/0000-0003-1134-0564)
- Jayasinghe Rg
- Isabella Saldarriaga
- Nick Pabustan (ORCID: https://orcid.org/0009-0001-1996-3048)
- Krista Angeliadis
- Vernadette A Simon
- Jarod Morgenroth-Rebin
- Emir Radkevich
- William C. Pilcher
- Eric Anderson
- Sagar Lonial
- Shaji Kumar
- Laura Walker
- Ravi Vij
- Roderick Lin
- Igor Figueiredo
- Song Cao
- Nikolaos Kalavros
- Yizhe Song
- Junia Vieira Dos Santos
- Geoffrey Kelly
- Darwin D’Souza
- Chiang I-ling
- Madhav V. Dhodapkar
- Manoj Bhasin
- Kai Nie
- April Cook
- Li Ding
- Sacha Gnjatic
- I-ling Chiang
- Beena E. Thomas
- Edgar Gonzalez-Kozlova
- Jennifer Rogers
- Zhihong Chen
- Ioannis S. Vlachos
- Matthew A. Wyczalkowski
- Stephen T. Oh
- Nicolas F. Fernandez
- John Leech
- Ying Li
- Lijun Yao
- George Mulligan
- Mark Hamilton
- Surendra Dasari
- Michael P. Rettig
- Swati S. Bhasin
- Marina E. Michaud
- Seunghee Kim-Schulze
- Julia T. Wang
Institutions
- Broad Institute (US)
- Georgia Institute of Technology (US)
- Beth Israel Deaconess Medical Center (US)
- Emory Healthcare (US)
- Harvard University (US)
- Emory University (US)
- Emory and Henry College (US)
- Washington University in St. Louis (US)
- Multiple Myeloma Research Foundation (US)
- Aflac (United States) (US)
- Mayo Clinic in Arizona (US)
- Tisch Hospital (US)
- Children's Healthcare of Atlanta (US)
- Winship Cancer Institute
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Nature Cancer
- Published
- 2026-01-09
- DOI
- https://doi.org/10.1038/s43018-025-01072-4
- Citations
- 1
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 35.41