JCI：中山大学潘景轩教授找到可能彻底治愈常见白血病的新靶点

2016-09-22 佚名生物谷

近日，来自中国中山大学的潘景轩教授带领研究团队在慢性髓性白血病（CML）的治疗靶点开发方面取得重要进展，他们发现甲基转移酶PRMT5是维持白血病干细胞存活和自我更新的重要因子，该研究成果有望推动对CML彻底治愈的进程。对CML治疗药物伊马替尼不敏感的白血病干细胞被认为是CML抵抗BCR-ABL酪氨酸激酶抑制剂以及出现疾病复发的主要原因。发现新治疗靶点，清除白血病干细胞可能是治愈CML的一种

近日，来自中国中山大学的潘景轩教授带领研究团队在慢性髓性白血病（CML）的治疗靶点开发方面取得重要进展，他们发现甲基转移酶PRMT5是维持白血病干细胞存活和自我更新的重要因子，该研究成果有望推动对CML彻底治愈的进程。

对CML治疗药物伊马替尼不敏感的白血病干细胞被认为是CML抵抗BCR-ABL酪氨酸激酶抑制剂以及出现疾病复发的主要原因。发现新治疗靶点，清除白血病干细胞可能是治愈CML的一种策略。

在这项研究中，研究人员在CML细胞中发现BCR-ABL和蛋白质精氨酸甲基转移酶5（PRMT5）之间存在一个正反馈回路。他们观察到人类CML白血病干细胞中存在PRMT5过表达的现象。之后研究人员利用shRNA对PRMT5的基因表达进行沉默，也利用小分子抑制剂PJ-68阻断PRMT5的甲基转移酶活性，均发现能够降低来自CML病人的白血病干细胞的存活，抑制长期培养起始细胞。

更进一步的研究表明，降低PRMT5表达或用抑制剂抑制其活性能够显著延长CML小鼠模型的生存时间，损伤移植到体内的CML白血病干细胞在体内的自我更新能力。除此之外PJ-68还会抑制人类CML CD34+细胞在免疫缺陷小鼠体内的长期移植效果。研究人员还发现抑制PRMT5能够通过减少DVL3蛋白干扰Wnt/b-catenin信号途径在CML CD34+细胞中的作用。

这项研究表明对组蛋白精氨酸残基的甲基化修饰是控制白血病干细胞自我更新的一种可调控机制，因此PRMT5有望成为对抗白血病干细胞的一个潜在治疗靶点。

原始出处

Yanli Jin,1 Jingfeng Zhou,1 Fang Xu,1 Bei Jin,1 Lijing Cui,2 Yun Wang,1 Xin Du,3 Juan Li,4 Peng Li,5 Ruibao Ren,6 and Jingxuan Pan.Targeting methyltransferase PRMT5 eliminates leukemia stem cells in chronic myelogenous leukemia.JCI.2016

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2017-03-20 caobinglei8079

#JCI#

35 0
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2016-10-11 童小孩

太棒了

76 0
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2016-09-30 thlabcde

太好了！

81 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-24 lsndxfj

#新靶点#

32 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-24 kalseyzl

#中山大学#

35 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-24 葵花是个叒女子-c

好牛逼～～～～～～

77 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-23 shuihanli

到临床还有一段距离！！！

78 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-23 simayunhe

不错，一大突破！恭喜科研

70 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-23 知难而进

继续关注！

31 0
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authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160811/IMG57AC91915ACA64463.jpg, createdBy=9c351934462, createdName=知难而进, createdTime=Fri Sep 23 16:22:00 CST 2016, time=2016-09-23, status=1, ipAttribution=)]
2016-09-23 知难而进

谢谢分享！

29 0

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