Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia
Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia
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DOI：
10.1007/s13277-016-4983-4
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Qiuhua Zhu;Lingxiu Zhang;Xiaodong Li;Fang Chen;Ling Jiang;Guopan Yu;Zhi-xiang Wang;C. Yin;Xuejie Jiang;Q. Zhong;Hong-sheng Zhou;B. Ding;Chunli Wang;F. Meng
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文献类型：
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作者：
Qiuhua Zhu;Lingxiu Zhang;Xiaodong Li;Fang Chen;Ling Jiang;Guopan Yu;Zhi-xiang Wang;C. Yin;Xuejie Jiang;Q. Zhong;Hong-sheng Zhou;B. Ding;Chunli Wang;F. Meng
越来越多的证据表明，ZEST同源增强子2(EZH2)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)中的作用尚未得到深入研究。在本研究中，我们调查了EZH2和EMI之间可能的关联。我们发现AML患者EZH2的信使RNA和蛋白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，在急性髓系白血病患者中，EZH基因表达与外周血母细胞百分率呈正相关(r= 0.404，p= 0.009)。高表达EZH2的KASUMI-1和HL-60细胞的迁移能力明显高于U937和KG-1α。相反，沉默EZH2导致细胞增殖和迁移能力降低，细胞凋亡率增加。后者伴随着相关蛋白p-ERK、p-cMYC和基质金属蛋白酶2(MMP2)的表达减少和上皮钙粘附素(E-cadherin)的增加。提示EZH2的高表达可能与急性髓系白血病髓外浸润有关，并通过激活p-ERK/p-cMYC/MMP-2和E-cadherin信号通路影响其发病机制。
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 betweenEZH2mRNA 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.