The microenvironment in myelodysplastic syndromes: Niche-mediated disease initiation and progression.
The microenvironment in myelodysplastic syndromes: Niche-mediated disease initiation and progression.
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DOI：
10.1016/j.exphem.2017.08.003
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发表时间：
2017-11
影响因子：
2.6
通讯作者：
Calvi LM
中科院分区：
文献类型：
--
作者：
Li AJ;Calvi LM
骨髓增生异常综合征(MDS)是一种造血干/祖细胞的克隆性疾病，是导致获得性骨髓衰竭的最常见原因。MDS以无效的造血、骨髓发育异常和转化为急性白血病的风险为特征，仍然是一种治疗不当的疾病。尽管识别人类MDS的造血异常对我们理解MDS的发病机制有很大贡献，但现在的证据表明，骨髓微环境(BMME)是疾病发生和发展的另一个关键因素。随着对骨髓微环境的进一步了解，我们开始研究造血小生境在MDS中的作用。尽管MDS的遗传多样性，但MDS和BMME之间的相互作用似乎是一种常见的疾病特征，因此代表着一个吸引人的治疗靶点。需要进一步了解MDS和其生态位之间的相互依赖关系，以描绘导致造血衰竭的机制以及如何将微环境作为临床靶点。这篇综述将提供来自人类MDS和小鼠模型的数据概述，这些数据支持BMME功能障碍在疾病发病的几个步骤中所起的作用。虽然到目前为止还没有模型或人类研究结合所有这些发现，但我们将回顾目前确定骨髓微环境参与MDS发病的每一步的数据，组织这些数据以反映正常造血系统变得骨髓异常增生和MDS进展到骨髓衰竭和转化时BMME的贡献时间顺序。尽管微环境的异质性和功能障碍肯定会增加这种综合征的复杂性，但数据已经表明，靶向微环境信号可能代表着MDS治疗的新治疗策略。
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although identification of hematopoietic aberrations in human MDS has contributed significantly to our understanding of MDS pathogenesis, evidence now identify the bone marrow microenvironment (BMME) as another key contributor to disease initiation and progression. With improved understanding of the BMME, we are beginning to refine the role of the hematopoietic niche in MDS. Despite genetic diversity in MDS, interaction between MDS and the BMME appears to be a common disease feature, and therefore represents an appealing therapeutic target. Further understanding of the interdependent relationship between MDS and its niche is needed to delineate the mechanisms underlying hematopoietic failure and how the microenvironment can be clinically targeted. This review will provide an overview of data from human MDS and murine models supporting a role for BMME dysfunction at several steps of disease pathogenesis. While no models or human studies so far have combined all these findings, we will review current data identifying BMME involvement in each step of MDS pathogenesis, organized to reflect the chronology of BMME contribution as the normal hematopoietic system becomes myelodysplastic and MDS progresses to marrow failure and transformation. Although microenvironmental heterogeneity and dysfunction certainly add complexity to this syndrome, data are already demonstrating that targeting microenvironmental signals may represent novel therapeutic strategies for MDS treatment.
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影响因子：
6.2
作者：
Aguayo, A;Kantarjian, HM;Albitar, M
通讯作者：
Albitar, M
影响因子：
20.3
作者：
Bellamy, WT;Richter, L;List, AF
通讯作者：
List, AF
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20.3
作者：
Aguayo, A;Kantarjian, H;Albitar, M
通讯作者：
Albitar, M
影响因子：
2.6
作者：
Cortelezzi, A;Fracchiolla, NS;Deliliers, GL
通讯作者：
Deliliers, GL
影响因子：
20.3
作者：
Aguayo, A;Estey, E;Albitar, M
通讯作者：
Albitar, M