The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia.
The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia.
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DOI：
10.1038/nrc.2016.112
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Ebert BL
中科院分区：
文献类型：
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作者：
Sperling AS;Gibson CJ;Ebert BL
骨髓增生异常综合征(MDS)是一种由突变的造血干细胞扩增引起的克隆性疾病。在从不确定潜能克隆性造血(CHIP)到继发性急性髓系白血病(SAML)的一系列髓系疾病中，MDS的区别在于存在外周血红细胞减少，造血分化异常，缺乏定义急性白血病的特征。超过50个重复突变的基因参与了MDS的发病机制，包括编码参与前mRNA剪接、表观遗传调节和转录的蛋白的基因。在这篇综述中，我们讨论了导致CHIP和进一步向MDS和SAML克隆进化的分子过程。我们还强调了这些见解如何塑造MDS的临床管理，包括分类方案、预后评分系统和治疗方法。
Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated hematopoietic stem cells. In a spectrum of myeloid disorders ranging from clonal hematopoiesis of indeterminate potential (CHIP) to secondary acute myeloid leukemia (sAML), MDS is distinguished by the presence of peripheral blood cytopenias, dysplastic hematopoietic differentiation, and the absence of features that define acute leukemia. Over 50 recurrently mutated genes are involved in the pathogenesis of MDS, including genes that encode proteins involved in pre-mRNA splicing, epigenetic regulation, and transcription. In this review we discuss the molecular processes that lead to CHIP and further clonal evolution to MDS and sAML. We also highlight the ways in which these insights are shaping the clinical management of MDS, including classification schemata, prognostic scoring systems, and therapeutic approaches.