Like normal hematopoietic stem cells, leukemic stem cells depend on their bone marrow (BM) microenvironment for survival, but the underlying mechanisms remain largely unknown. We have studied the contribution of nestin⁺ BM mesenchymal stem cells (BMSCs) to MLL-AF9-driven acute myeloid leukemia (AML) development and chemoresistance in vivo. Unlike bulk stroma, nestin⁺ BMSC numbers are not reduced in AML, but their function changes to support AML cells, at the expense of non-mutated hematopoietic stem cells (HSCs). Nestin⁺ cell depletion delays leukemogenesis in primary AML mice and selectively decreases AML, but not normal, cells in chimeric mice. Nestin⁺ BMSCs support survival and chemotherapy relapse of AML through increased oxidative phosphorylation, tricarboxylic acid (TCA) cycle activity, and glutathione (GSH)-mediated antioxidant defense. Therefore, AML cells co-opt energy sources and antioxidant defense mechanisms from BMSCs to survive chemotherapy.

与正常的造血干细胞一样，白血病干细胞的生存依赖于其骨髓 (BM) 微环境，但其潜在机制在很大程度上仍不为人知。^{我们研究了巢蛋白+} BM 间充质干细胞 (BMSC) 对 MLL-AF9 驱动的急性髓性白血病 (AML) 发展和体内化学耐药性的贡献。与大块基质不同，巢蛋白⁺ BMSC 数量在 AML 中并未减少，但它们的功能发生变化以支持 AML 细胞，但以牺牲未突变的造血干细胞 (HSC) 为代价。Nestin ⁺细胞耗竭会延迟原发性 AML 小鼠的白血病生成，并选择性地减少嵌合小鼠中的 AML 细胞，但不会减少正常细胞。巢蛋白⁺BMSCs 通过增加氧化磷酸化、三羧酸 (TCA) 循环活性和谷胱甘肽 (GSH) 介导的抗氧化防御来支持 AML 的存活和化疗复发。因此，AML 细胞选择 BMSC 的能量来源和抗氧化防御机制以在化疗中存活。