骨髓微环境与骨髓增生异常综合征

骨髓增生异常综合征 （MDS） 是一组起源于造血干细胞 （HSC） 的异质性克隆性疾病， 特点是髓系细胞一系或多系发育异常， 表现为无效造血、 外周血细胞减少， 高风险向急性髓系白血病 （AML） 转化。MDS的发病、 造血功能改变及预后与骨髓微环境密切相关。骨髓微环境是一个复杂的网络系统， 其中基质细胞包括间充质干细胞的形态和功能异常、 成骨细胞分化受损、 血管内皮细胞数量增加、 单核/巨噬细胞数量减少都会促进MDS发病； 细胞因子如肿瘤坏死因子-α （TNF-α） 过表达、 血管内皮生长因子 （VEGF） 及基质细胞衍生因子-1 （SDF-1） 表达异常也与MDS发病密切相关； 基因如Dicer1低表达、 AURKA高表达、 SPINT2低表达均会促进MDS发病； Wnt/β-catenin信号通路的异常激活、 异常的PI3K/AKT及Hh信号通路也参与MDS的发病、 进展。对MDS和骨髓微环境相互作用的研究， 将进一步阐明该病的发病机制、 进展和预后， 并有助于靶向治疗的发展。本文就MDS中骨髓微环境基质细胞、 细胞因子、 基因、 信号通路异常的研究进展进行综述。

Bone marrow microenvironment and myelodysplastic syndrome

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders originating from hematopoietic stem cells (HSC), characterized by unilineage or multilineage dysplasia of myeloid cells, ineffective hematopoiesis, peripheral blood cytopenias and high risk of transform into acute myeloid leukemia (AML). The pathogenesis, hematopoietic function change and prognosis of MDS are closely related to the bone marrow microenvironment. Bone marrow microenvironment is a complex network system, among them, stromal cells including abnormal morphology and function of mesenchymal stem cells, impaired osteoblast differentiation, increased number of vascular endothelial cells, and decreased number of monocytes /macrophages can promote the pathogenesis of MDS. The abnormal expression of cytokines such as tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) are also closely related to the pathogenesis of MDS. Low expression of genes such as Dicer1, high expression of AURKA, and low expression of SPINT2 all contribute to the pathogenesis of MDS. Aberrant activation of Wnt/β-catenin signaling pathways, abnormal PI3K/AKT and Hh signaling pathways are also involved in the pathogenesis and progression of MDS. The study of the interaction between MDS and bone marrow microenvironment will further elucidate the pathogenesis, progress and prognosis of the disease, and will contribute to the development of targeted therapy. This review provides the research progress of bone marrow microenvironment stromal cells, cytokines, genes, and signaling pathway abnormalities in MDS.