[核因子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].

作者信息

Wang Wei-Li, Xu Qiao-Zhu, Mu Xiao-Huan, Wang Le, Zhang Li-Yan, Xu Jing, Gao Ying-Dai, Cheng Tao, Yuan Wei-Ping

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 30020, China.

State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 30020, China. E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1622-1626. doi: 10.7534/j.issn.1009-2137.2016.06.002.

DOI:10.7534/j.issn.1009-2137.2016.06.002

PMID:28024466

Abstract

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 up-regulated genes, EDARADD, TNFSF14, could activate the NF-κB signal pathway, IL6 could regulate the inflammatory signal. The down-regulated genes, TNFRSF 10B, 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.

摘要

目的

探讨核因子κB（NF-κB）抑制剂在急性髓系白血病（AML）发生发展中的作用。

方法

收集8例AML患者及8例正常人的AML和正常骨髓样本。采用NF-κB PCR芯片检测NF-κB信号通路基因的表达。然后，构建AML小鼠模型以检测NF-κB抑制剂在AML中的作用。

结果

AML患者中NF-κB信号通路被激活。上调基因EDARADD、TNFSF14可激活NF-κB信号通路，IL6可调节炎症信号。下调基因TNFRSF 10B、TNFRSF1A可导致细胞凋亡。成功构建了AML小鼠模型。随后给予NF-κB抑制剂可减少白血病龛对正常造血干细胞（HSCs）的抑制，促进HSC进入细胞周期。