RIP1缺失或突变减弱MLL-AF9白血病细胞致病能力

RIP1 deletion or mutation attenuates the pathogenicity of MLL-AF9 leukemia stem cells

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.

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.