Xenium in situ generates the first map of human bone marrow in myeloma
Impact at a glance: Researchers leveraged Xenium single cell spatial imaging in a difficult-to-study sample type, bone marrow trephines, to access a structural view of the bone marrow microenvironment in multiple myeloma. They observed surprising spatial and compositional heterogeneity among diagnosed myeloma samples, challenging the current hypothesis that a universal bone marrow microenvironment drives malignant plasma cell proliferation (1).
It’s become intuitive to expect that spatial composition, heterogeneity, and local cellular relationships in solid tumors are critical factors affecting disease progression and therapeutic response and resistance. But how do you discern the impact of these critical factors in liquid tumors?
Researchers from the The Walter and Eliza Hall Institute of Medical Research in Australia and the University of Melbourne came together to solve this problem in multiple myeloma, a blood cancer that results from uncontrolled proliferation of plasma cells in the bone marrow (1).
But bone marrow isn’t an easy sample to study from a spatial perspective. It’s typically extracted as a liquid biopsy through bone marrow aspiration. However, through an optimized formalin fixation protocol, the research team was able to study trephines (small, solid cores of bone tissue containing the marrow) using Xenium spatial transcriptomics technology.
They validated this platform on one trephine sample treated with their protocol using a pre-designed 377-gene human multi-tissue and cancer panel. This approach confirmed the presence of expected hematopoietic and stromal cells with cell-type labels defined by an scRNA-seq dataset, as well as plasma cells and other tissue structures. From this feasibility study, they moved on to profile 21 trephine samples from controls, individuals with premalignant disease, and individuals with diagnosed multiple myeloma using the 5,001-gene Xenium Prime 5K human pan-tissue and pathways panel.
This first-of-its-kind, comprehensive spatial atlasing of bone marrow trephine samples yielded some unexpected results. First, it revealed a pattern of heterogeneous cancer cell distribution. Trephines were either occupied entirely by one predominant plasma cell cluster or they were scattered with spatially restricted plasma cell subpopulations that had distinct gene expression signatures. Spatial neighborhood analysis further demonstrated that distinct plasma cell subpopulations resided in transcriptionally and compositionally unique intratumoral neighborhoods. For example, plasma cell subpopulations with an inflammatory phenotype were enriched in regions with a high T-cell density.
The team’s findings oppose a core dogma of hematopoietic tumor biology—that malignant cells, in this case plasma cells, form a universal, disease-specific microenvironment conducive to disease progression. However, it appears that distinct plasma cell subpopulations remodel local bone marrow microenvironments in different ways, offering a new paradigm to understand multiple myeloma malignancy.
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References:
- Yip R, et al. Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics. Blood 146: 1837–1849 (2025). doi: 10.1182/blood.2025028896
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