Inflammatory bone marrow microenvironment
Inflammatory bone marrow microenvironment
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DOI：
10.1182/hematology.2019000045
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发表时间：
2019-12-01
影响因子：
3
通讯作者：
Schneider, Rebekka K.
中科院分区：
文献类型：
--
作者：
Leimkuhler, Nils B.;Schneider, Rebekka K.
自我更新的造血干细胞及其后代，谱系特异性的下游祖细胞，在骨髓(BM)中维持稳定的造血。近年来越来越多的证据表明，不仅原始的造血干细胞和祖细胞(HSPC)，而且定义骨髓(BM)微环境的细胞都能感受到造血应激信号。它们不仅通过细胞内的机制，而且通过细胞-外在的机制来指挥和协调造血。炎症通过激活免疫系统在组织修复中和作为一种防御机制发挥许多有益的作用。然而，慢性炎症可能会对HSPC造成不利影响，导致细胞(DNA)损伤，导致骨髓衰竭，甚至导致白血病。新的数据表明，骨髓微环境在血液系统恶性肿瘤的发病机制中起着重要作用，特别是通过破坏炎症信号，特别是在微环境细胞中。在微环境改变的背景下，克隆选择可以在毒性侮辱(例如，化疗)的背景下发生，不仅是衰老，还包括炎症。在这篇综述中，我们总结了导致炎性骨髓微环境的机制，并讨论了这如何影响正常的造血。我们特别关注衰老的过程，众所周知，衰老涉及低度炎症，也与年龄相关的克隆性造血和潜在的恶性转化有关。
Self-renewing hematopoietic stem cells and their progeny, lineage-specific downstream progenitors, maintain steady-state hematopoiesis in the bone marrow (BM). Accumulating evidence over the last few years indicates that not only primitive hematopoietic stem and progenitor cells (HSPCs), but also cells defining the microenvironment of the BM (BM niche), sense hematopoietic stress signals. They respond by directing and orchestrating hematopoiesis via not only cell-intrinsic but also cell-extrinsic mechanisms. Inflammation has many beneficial roles by activating the immune system in tissue repair and as a defense mechanism. However, chronic inflammation can have detrimental effects by stressing HSPCs, leading to cell (DNA) damage resulting in BM failure or even to leukemia. Emerging data have demonstrated that the BM microenvironment plays a significant role in the pathogenesis of hematopoietic malignancies, in particular, through disrupted inflammatory signaling, specifically in niche (microenvironmental) cells. Clonal selection in the context of microenvironmental alterations can occur in the context of toxic insults (eg, chemotherapy), not only aging but also inflammation. In this review, we summarize mechanisms that lead to an inflammatory BM microenvironment and discuss how this affects normal hematopoiesis. We pay particular attention to the process of aging, which is known to involve low-grade inflammation and is also associated with age-related clonal hematopoiesis and potentially malignant transformation.