Selective endosteal remodeling of blood vessels in acute myeloid leukemia promotes malignancy at the expense of hematopoietic stem cells
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Hematopoietic stem cell (HSC) function requires bone marrow vascular niches, which have been proposed to be co-opted by leukemia cells to support their propagation. Acute myeloid leukemia (AML) cells produce angiogenic factors; however, anti-angiogenic therapies have not improved AML patient outcome. Using intravital microscopy we uncovered hierarchical vascular remodeling with AML progression. AML cells outcompete non-malignant hematopoiesis by gradual elimination of stroma cells, endosteal endothelium, and osteoblastic cells. While central marrow remains vascularized and splenic vascular niches expand, the remodeled endosteal regions lose the ability to retain HSCs. Overall, the endosteal endothelium microenvironment is altered by AML, yet by preserving it we rescue HSC loss and promote chemotherapeutic efficacy. Our findings suggest therapies targeting the endosteal vasculature may improve existing AML therapeutic regimes.
提供机构：
The Walter and Eliza Hall Institute of Medical Research
创建时间：
2022-02-20
