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High expression of ABCG2 induced by EZH2 disruption has pivotal roles in MDS pathogenesis.
Leukemia ( IF 12.8 ) Pub Date : 2018-02-01 , DOI: 10.1038/leu.2017.227
K C Kawabata , Y Hayashi , D Inoue , H Meguro , H Sakurai , T Fukuyama , Y Tanaka , S Asada , T Fukushima , R Nagase , R Takeda , Y Harada , J Kitaura , S Goyama , H Harada , H Aburatani , T Kitamura

Both proto-oncogenic and tumor-suppressive functions have been reported for enhancer of zeste homolog 2 (EZH2). To investigate the effects of its inactivation, a mutant EZH2 lacking its catalytic domain was prepared (EZH2-dSET). In a mouse bone marrow transplant model, EZH2-dSET expression in bone marrow cells induced a myelodysplastic syndrome (MDS)-like disease in transplanted mice. Analysis of these mice identified Abcg2 as a direct target of EZH2. Intriguingly, Abcg2 expression alone induced the same disease in the transplanted mice, where stemness genes were enriched. Interestingly, ABCG2 expression is specifically high in MDS patients. The present results indicate that ABCG2 de-repression induced by EZH2 mutations have crucial roles in MDS pathogenesis.

中文翻译:

EZH2破坏诱导的ABCG2的高表达在MDS发病机理中起着关键作用。

据报道,zeste同源物2(EZH2)的增强子具有原癌和抑癌功能。为了研究其失活的影响,制备了缺少其催化结构域的突变体EZH2(EZH2-dSET)。在小鼠骨髓移植模型中,骨髓细胞中EZH2-dSET的表达诱导了移植小鼠的骨髓增生异常综合症(MDS)样疾病。这些小鼠的分析确定Abcg2为EZH2的直接靶标。有趣的是,单独的Abcg2表达在移植小鼠中诱发了相同的疾病,其中干性基因得到了丰富。有趣的是,ABCG2表达在MDS患者中特别高。目前的结果表明,由EZH2突变引起的ABCG2抑制在MDS发病机理中起着至关重要的作用。
更新日期:2017-09-08
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