{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:56:36Z","timestamp":1793656596271,"version":"4.5.1"},"posted":{"date-parts":[[2026,3,25]]},"group-title":"Cancer Biology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Myeloma Solutions Fund"},{"award":["R01 CA252222"],"award-info":[{"award-number":["R01 CA252222"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA244899"],"award-info":[{"award-number":["R01 CA244899"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 CA262754"],"award-info":[{"award-number":["R01 CA262754"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["K12 CA270375"],"award-info":[{"award-number":["K12 CA270375"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA196521"],"award-info":[{"award-number":["CA196521"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/03ww1bx13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Multiple myeloma (MM) is a plasma cell malignancy shaped by dynamic interactions between MM cells and non-malignant cells in the immune microenvironment. To spatially profile the influence of cellular context on MM and immune cell expression, we developed a multimodal framework integrating 10x Genomics Visium HD, 10x Genomics Xenium, and clinically annotated single-cell RNA (scRNA-seq) sequencing datasets. Visium HD enabled unbiased, whole transcriptome, spatial discovery at 16 \u00b5m resolution, Xenium provided orthogonal validation at single-cell resolution, and scRNA-seq extended findings by mapping spatial labels and leveraging the greater sequencing depth. We developed a custom framework for cell type annotation within Visium HD spatial bins. Our approach enabled identification of plasma cell-dense niches enriched for non-canonical Wnt signaling, associated with gene expression supporting cell adhesion mediated drug resistance, inferior progression-free survival, and extramedullary lesions. Immune cells within these neighborhoods exhibited suppressed transcriptional states, including increased inhibitory receptor expression such as\n                  <jats:italic>LAG3<\/jats:italic>\n                  . Utilizing the niche-driven transcriptional states in MM and immune cells, we were able to develop a 15-gene signature independently predictive of progression free survival (HR = 2.00, p &lt; 0.0001). Collectively, this study demonstrates the potential of integrated spatial and single-cell transcriptomics to define niche-specific programs supporting MM progression.\n                <\/jats:p>","DOI":"10.64898\/2026.03.23.713195","type":"posted-content","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:20:48Z","timestamp":1774498848000},"source":"Crossref","is-referenced-by-count":4,"title":["Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions"],"prefix":"10.64898","author":[{"given":"Denis J","family":"Ohlstrom","sequence":"first","affiliation":[{"name":"Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA"},{"name":"Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina 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