Department of Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, New York, New York 10032.
Cold Spring Harb Perspect Med. 2018 Jul 2;8(7):a031328. doi: 10.1101/cshperspect.a031328.
Hematopoietic stem cells (HSCs) interact dynamically with an intricate network of cells in the bone marrow (BM) microenvironment or niche. These interactions provide instructive cues that influence the production and lineage determination of different types of blood cells and maintenance of HSC quiescence. They also contribute to hematopoietic deregulation and hematological myeloid malignancies. Alterations in the BM niche are commonly observed in myeloid malignancies and contribute to the aberrant function of myelodysplastic and leukemia-initiating stem cells. In this work, we review how different components of the BM niche affect normal hematopoiesis, the molecular signals that govern this interaction, and how genetic changes in stromal cells or alterations in remodeled malignant BM niches contribute to myeloid malignancies. Understanding the intricacies between normal and malignant niches and their modulation may provide insights into developing novel therapeutics for blood disorders.
造血干细胞（HSCs）与骨髓（BM）微环境或龛中的复杂细胞网络动态相互作用。这些相互作用提供了影响不同类型血细胞的产生和谱系决定以及 HSC 静止的有指导意义的线索。它们还有助于造血失调和血液髓系恶性肿瘤。BM 龛中的改变在髓系恶性肿瘤中很常见，并导致骨髓增生异常和白血病起始干细胞的异常功能。在这项工作中，我们回顾了 BM 龛的不同成分如何影响正常造血、控制这种相互作用的分子信号，以及基质细胞中的遗传改变或恶性 BM 龛的改变如何导致髓系恶性肿瘤。了解正常和恶性龛之间的复杂性及其调节可能为开发血液疾病的新疗法提供思路。
