Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics

Yip, RKH; Er, J; Qin, L; Nguyen, QH; Motyer, A; Rimes, JS; Light, A; Mishi, RD; Ling, L; Anttila, CJA; Tsui, E; Amann-Zalcenstein, D; Dowling, MR; Rogers, KL; Bowden, R; Chen, Y; Harrison, SJ; Hawkins, ED

Author(s): Yip, RKH; Er, J; Qin, L; Nguyen, QH; Motyer, A; Rimes, JS; Light, A; Mishi, RD; Ling, L; Anttila, CJA; Tsui, E; Amann-Zalcenstein, D; Dowling, MR; Rogers, KL; Bowden, R; Chen, Y; Harrison, SJ; Hawkins, ED;
Details: Publication Year 2025-10-09,Volume 146,Issue #15,Page 1837-1849
Journal Title: Blood
Abstract: The bone marrow microenvironment is intimately linked to the biology that underpins the development and progression of multiple myeloma. However, the complex cellular and molecular features that form bone marrow niches are poorly defined. Here, we used subcellular spatial transcriptomics to profile the expression of 5001 genes in human bone marrow in the context of multiple myeloma. Using this approach, we explored the plasma cell and stroma ecosystem in bone marrow trephine biopsy specimens (herein referred to as trephines) from 21 individuals, including 7 with premalignant disease and 10 with newly diagnosed multiple myeloma. Using spatial transcriptomics in conjunction with an optimized trephine biobanking methodology, we could resolve major components of the human bone marrow microenvironment and reliably characterize distinct plasma cell populations in samples from healthy, premalignant disease and active myeloma. When plasma cells were visualized in the context of location, we detected spatially restricted subpopulations of plasma cells in 5 of 10 newly diagnosed myeloma trephines. Surprisingly, the composition of hematopoietic and stromal microenvironments varied significantly between newly diagnosed myeloma trephines. Furthermore, these differences in microenvironments were also observed within trephines that had spatially restricted plasma cell subpopulations. Thus, these data are not consistent with the hypothesis that a universal bone marrow microenvironment supports the expansion of malignant plasma cells in myeloma. Instead, we propose that myeloma subpopulations form distinct microenvironments and can vary both between patients and spatial locations.
Publisher: American Society of Hematology
Keywords: Humans; *Multiple Myeloma/pathology/genetics/metabolism; *Bone Marrow/pathology/metabolism; *Transcriptome; *Tumor Microenvironment; Biopsy; Plasma Cells/pathology/metabolism; Gene Expression Profiling; Female; Male; Middle Aged; Aged
Department(s): Laboratory Research; Haematology
Publisher's Version: https://doi.org/10.1182/blood.2025028896
Open Access at Publisher's Site: https://doi.org/10.1182/blood.2025028896
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-08-19 12:59:42

Last Modified: 2025-11-25 12:06:39