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During leukemic progression, we observed an expansion of myeloid and progenitor cell populations, increased PD-L1\n                  <jats:sup>+<\/jats:sup>\n                  leukemic cells, the upregulation of PD-1 on CD4\n                  <jats:sup>+<\/jats:sup>\n                  and CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, and a profound loss of B cells, plasma cells and bone cells. Advanced CML exhibited a striking expansion of immature, pericyte-deficient vasculature that disrupted vascular niches and impaired hematopoietic stem\/progenitor cell positioning. Spatial mapping revealed leukemia-specific cellular neighborhoods enriched in PD-1\n                  <jats:sup>+<\/jats:sup>\n                  CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cells, suggesting localized immune cell exhaustion. Early-stage CML showed increaseds between plasmacytoid dendritic cells and megakaryocytes, whereas advanced CML featured heightened megakaryocyte emperipolesis of non-leukemic granulocytes. Megakaryocytes were morphologically irregular in CML mice and BM trephine biopsies from CML patients. Laser-capture microdissected megakaryocytes from newly diagnosed CML patients had reduced expression of cytoskeleton genes, which was reversed in advanced cases treated with tyrosine kinase inhibitors. 3D imaging revealed vascular disorganization and depleted megakaryocytes in the diaphysis, underscoring region-specific pathology. Together, this study provides a spatiotemporal single-cell atlas of the BMME during leukemic progression, showing how leukemic cells reprogram the niche to support their expansion and immune evasion.\n                <\/jats:p>","DOI":"10.1101\/2025.09.27.678113","type":"posted-content","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T23:15:17Z","timestamp":1759187717000},"source":"Crossref","is-referenced-by-count":1,"title":["High-Dimensional Spatiotemporal Single-Cell and 3D Atlas of the Bone Marrow Microenvironment during Leukemic Progression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5394-2285","authenticated-orcid":false,"given":"Lanzhu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC 2180) \u201cImage-Guided and Functionally Instructed Tumor 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