Authors
William C Pilcher, Hongwei Tang, Katherine Ferguson, Steven M Foltz, Marina E Michaud, Sarthak Satpathy, Nishi Nilesh Shah, Yuxin Jin, Denis Ohlstrom, Mojtaba Bakhtiari, Chaitanya R Acharya, Immune Atlas Consortium, Alexander M Gout, Jonathan Keats, Madhav V Dhodapkar, David E Avigan, Ravi Vij, Shaji K Kumar, Hearn Jay Cho, Ioannis S Vlachos, Li Ding, Sacha Gnjatic, Craig Emmitt Cole, Ajay K Nooka, Sagar Lonial, John Carpten, George Mulligan, Linda B Baughn, Manoj Bhasin
Published in
Blood. Oct 05, 2026. Epub Oct 05, 2026.
Abstract
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.
PMID:
42832384
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.
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