| 摘要: |
| 通过克隆形成能力实验以及体内移植实验，发现当敲除小鼠MLL-AF9细胞中的受体结合蛋白1（RIP1）基因后，相对于WT MLL-AF9细胞，其克隆形成能力明显减弱，移植后小鼠生存时间延长了3倍以上.在组织切片观察中，WT MLL-AF9细胞移植小鼠出现明显白血病发病特征，而RIP1-/-MLL-AF9细胞移植小鼠的切片显示正常.当将RIP1中的激酶活性位点突变后，相对于WT MLL-AF9细胞，在移植实验中小鼠生存时间明显延长.对病发小鼠的脾脏细胞流式分析结果表明：激酶活性位点突变后致病能力明显减弱，提示RIP1基因的缺失会导致MLL-AF9致病能力减弱. |
| 关键词: 受体结合蛋白1(RIP1) MLL-AF9 克隆形成 生存时间 激酶活性 |
| DOI：10.3969/J.ISSN.1000-5137.2019.05.006 |
| 分类号:R733.71 |
| 基金项目:国家自然科学基金青年基金（81700141）；国家自然科学基金面上项目（81670151） |
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| RIP1 deletion or mutation attenuates the pathogenicity of MLL-AF9 leukemia stem cells |
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XU Zhaofeng, JIANG Yuyu, JIN Yujia, LI Jing
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College of Life Sciences, Shanghai Normal University, Shanghai 200234, China
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| Abstract: |
| In this article,by using the clonality assay and transplantation experiments in vivo,we found that the MLL-AF9 cells knocked out receptor-interating protein 1(RIP1) gene showed more weaken clonality,comparing with WT MLL-AF9 cells,and the survival experiments show the survival time of RIP1-/-(MLL-AF9) mice is extended more 3 times than WT MLL-AF9 mice after transplantation.The morphology of leukemia is observed in WT MLL-AF9 cells transplanted mice's tissue sections,while the sections of RIP1-/-MLL-AF9 cells are normal.When we mutate the kinase active sites in RIP1,the survival time of these mice is longer than the mice transplanted with WT MLL-AF9 cells.In the flow cytometry analysis of spleen cells of diseased mice,we found the mutations in the kinase active sites showed a significant decrease of pathogenicity.It is suggested that the deletion of the RIP1 gene leads to a decrease in the pathogenic ability of MLL-AF9 cells. |
| Key words: Receptor-Interacting Protein 1 (RIP1) MLL-AF9 clonality survival time kinase activity |
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