骨髓增生异常综合征的遗传学：从克隆性造血到继发性白血病

Sperling Adam S, Gibson Christopher J, Ebert Benjamin L

Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Nat Rev Cancer. 2017 Jan;17(1):5-19. doi: 10.1038/nrc.2016.112. Epub 2016 Nov 11.

Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated haematopoietic stem cells. In a spectrum of myeloid disorders ranging from clonal haematopoiesis of indeterminate potential (CHIP) to secondary acute myeloid leukaemia (sAML), MDS is distinguished by the presence of peripheral blood cytopenias, dysplastic haematopoietic differentiation and the absence of features that define acute leukaemia. More than 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.

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。在一系列从意义未明的克隆性造血（CHIP）到继发性急性髓系白血病（sAML）的髓系疾病中，MDS的特征是外周血细胞减少、造血分化异常以及缺乏定义急性白血病的特征。超过50个反复突变的基因参与了MDS的发病机制，包括编码参与前体mRNA剪接、表观遗传调控和转录的蛋白质的基因。在本综述中，我们讨论了导致CHIP以及进一步克隆进化为MDS和sAML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。