African Genetic Similarity Is Associated with Reduced Inflammation and Enhanced Adaptive Immunity in Multiple Myeloma
The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4⁺ T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14⁺ monocytes, increased CD16⁺ non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.
Authors
- Hearn Jay Cho (ORCID: https://orcid.org/0000-0003-4481-5757)
- Craig Emmitt Cole (ORCID: https://orcid.org/0000-0002-5537-761X)
- Mojtaba Bakhtiari (ORCID: https://orcid.org/0009-0007-6733-0070)
- William Pilcher (ORCID: https://orcid.org/0000-0002-8544-4967)
- Ajay K. Nooka (ORCID: https://orcid.org/0000-0003-4165-6869)
- Shaji Kunnathu Kumar (ORCID: https://orcid.org/0000-0001-5392-9284)
- Chaitanya R. Acharya (ORCID: https://orcid.org/0000-0001-7149-1749)
- Ravi Vij
- Linda Banovic Baughn (ORCID: https://orcid.org/0000-0001-5229-4897)
- Ioannis S. Vlachos (ORCID: https://orcid.org/0000-0002-8849-808X)
- Alexander M. Gout (ORCID: https://orcid.org/0000-0001-8943-5155)
- George Mulligan (ORCID: https://orcid.org/0009-0009-5084-9604)
- Nishi Shah (ORCID: https://orcid.org/0000-0002-4723-6745)
- David Avigan (ORCID: https://orcid.org/0000-0003-4624-6017)
- Yuxin Jin (ORCID: https://orcid.org/0000-0002-6124-9681)
- Marina E. Michaud (ORCID: https://orcid.org/0000-0003-0145-7320)
- Sarthak Satpathy (ORCID: https://orcid.org/0000-0002-8275-5989)
- Steven M. Foltz (ORCID: https://orcid.org/0000-0002-9526-8194)
- Sacha Gnjatic (ORCID: https://orcid.org/0000-0001-5643-9520)
- Jonathan J. Keats (ORCID: https://orcid.org/0000-0003-4375-7399)
- Madhav V. Dhodapkar (ORCID: https://orcid.org/0000-0002-8249-5988)
- Li Ding (ORCID: https://orcid.org/0000-0003-1517-2975)
- Hongwei Tang
- John Carpten
- Manoj Bhasin
- Katherine Ferguson
- Sagar Lonial
- Denis Ohlstrom
Institutions
- Translational Genomics Research Institute (US)
- City Of Hope National Medical Center (US)
- Georgia Institute of Technology (US)
- Beth Israel Deaconess Medical Center (US)
- Mayo Clinic (US)
- Harvard University (US)
- Emory University (US)
- Washington University in St. Louis (US)
- Multiple Myeloma Research Foundation (US)
- Fred Hutch Cancer Center (US)
- The Barbara Ann Karmanos Cancer Institute (US)
- City of Hope (US)
- Tisch Hospital (US)
- Beckman Research Institute
- Winship Cancer Institute
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Blood
- Published
- 2026-10-05
- DOI
- https://doi.org/10.1182/blood.2026033999
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00