NF-κB抑制剂在急性髓系白血病中的作用

Role of NF-κB inhibitor in Acute Myeloid Leukemia

目的:探讨NF-κB抑制剂在AML白血病发生发展过程中的作用。方法:随机收集16例骨髓标本,其中AML 8例,正常对照8例。应用PCR阵列检测NF-κB信号通路在AML中是否激活?同时构建小鼠白血病模型,检测NF-κB抑制剂对AML的作用。结果:NF-κB信号通路在AML中被激活,在高表达的基因中如EDARADD,TNFSF14可激活NF-κB通路,IL6介导炎症信号;在低表达的基因中如TNFRSF 10B,TNFRSF1A促进细胞凋亡。本实验成功构建了小鼠白血病模型。在小鼠白血病模型中给予NF-κB抑制剂,可缓解白血病微环境对正常造血干细胞的抑制作用,使正常造血干细胞进入细胞周期。结论:AML细胞中NF-κB信号通路被激活,NF-κB抑制剂促进正常造血干细胞细胞进入细胞周期。

Objective：To investigate the role of NF-κB inhibitor in occurence and development of AML.Methods：AML and normal bone marrow samples were collected from 8 AML patients and 8 normal persons.The expression of NF-κB signaling pathway genes was detected by NF-κB PCR array.Then,AML mouse model was constructed to test the role of NF-κB inhibitor in AML.Results：The NF-κB signal pathway was activated in AML patients.The upregulated genes,EDARADD,TNFSF14,could activate the NF-κB signal pathway,IL6 could regulate the inflammatory signal.The down-regulated genes,TNFRSF 10 B,TNFRSF1A,could lead to cell apoptosis.the AML mouse model was constructed successfully.Then administration of NF-κB inhibitor reduced the inhibition of leukemia niche to the normal hematopoietic stem cells（HSCs）,promoted the HSC to enter into cell cycle.Conclusion：The NF-κB signal pathway is activated in AML cells.AML mouse model is constructed successfully.NF-κB inhibitor has a potential to treat AML and promotes the HSC to enrter into cell cycle.