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EZH2表达水平升高与急性髓系白血病的髓外浸润相关。

Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia.

作者信息

Zhu Qiuhua, Zhang Lingxiu, Li Xiaodong, Chen Fang, Jiang Ling, Yu Guopan, Wang Zhixiang, Yin Changxin, Jiang Xuejie, Zhong Qingxiu, Zhou Hongsheng, Ding Bingjie, Wang Chunli, Meng Fanyi

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Hematopathy Diagnosis and Therapy Center, Kanghua Hospital, Dongguan, China.

出版信息

Tumour Biol. 2016 Aug;37(8):11409-20. doi: 10.1007/s13277-016-4983-4. Epub 2016 Mar 21.

Abstract

Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.

摘要

越来越多的证据表明,zeste同源物2增强子(EZH2)可促进实体瘤的转移能力,但EZH2在急性髓系白血病(AML)髓外浸润(EMI)中的作用尚未得到充分研究。在本研究中,我们调查了EZH2与EMI之间可能存在的关联。我们发现,AML患者中EZH2的信使核糖核酸(mRNA)和蛋白质表达水平均显著高于特发性血小板减少性紫癜(ITP)患者。此外,在AML患者中发现EZH2 mRNA表达与外周血原始细胞百分比呈正相关(r = 0.404,p = 0.009)。EZH2表达水平较高的Kasumi-1和HL-60的迁移能力明显高于U937和KG-1α。相反,EZH2沉默导致增殖和迁移能力降低以及凋亡增加。后一观察结果伴随着相关蛋白p-ERK、p-cmyc和基质金属蛋白酶2(MMP-2)表达降低以及上皮钙黏蛋白(E-钙黏蛋白)增加。这些数据表明,EZH2的高表达可能与急性髓系白血病的髓外浸润有关,并通过激活p-ERK/p-cmyc/MMP-2和E-钙黏蛋白信号通路影响发病机制。

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