Yip Raymond K H, Er Jeremy, Qin Lei, Nguyen Quoc Hoang, Motyer Allan, Rimes Joel S, Light Amanda, Mishi Ruvimbo D, Ling Ling, Anttila Casey J A, Tsui Ellen, Amann-Zalcenstein Daniela, Dowling Mark R, Rogers Kelly L, Bowden Rory, Chen Yunshun, Harrison Simon J, Hawkins Edwin D
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Blood. 2025 Jul 11. doi: 10.1182/blood.2025028896.
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 5,001 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 trephines from 21 individuals, including 7 with pre-malignant disease and 10 with newly diagnosed multiple myeloma. Using spatial transcriptomics in conjunction with an optimised trephine biobanking methodology, we could resolve major components of the human bone marrow microenvironment and reliably characterise distinct plasma cell populations in samples from healthy, pre-malignant disease and active myeloma. When plasma cells were visualised in the context of location, we detected spatially restricted subpopulations of plasma cells in five of ten newly diagnosed myeloma trephines. Surprisingly, the composition of haematopoietic 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 between both patients and spatial location.
骨髓微环境与多发性骨髓瘤发生发展的生物学机制密切相关。然而，构成骨髓龛的复杂细胞和分子特征仍不清楚。在此，我们使用亚细胞空间转录组学来分析多发性骨髓瘤背景下人类骨髓中5001个基因的表达。采用这种方法，我们研究了21名个体骨髓活检组织中的浆细胞和基质生态系统，其中包括7名患有癌前疾病的个体和10名新诊断的多发性骨髓瘤患者。通过将空间转录组学与优化的活检组织生物样本库方法相结合，我们能够解析人类骨髓微环境的主要成分，并可靠地表征来自健康、癌前疾病和活动性骨髓瘤样本中不同的浆细胞群体。当在位置背景下观察浆细胞时，我们在10例新诊断的骨髓瘤活检组织中的5例中检测到浆细胞的空间受限亚群。令人惊讶的是，新诊断的骨髓瘤活检组织中造血和基质微环境的组成存在显著差异。此外，在具有空间受限浆细胞亚群的活检组织中也观察到了这些微环境差异。因此，这些数据与普遍的骨髓微环境支持骨髓瘤中恶性浆细胞扩增的假设不一致。相反，我们提出骨髓瘤亚群形成不同的微环境，并且在患者和空间位置之间可能存在差异。
