Overexpression of MCM2 in myelodysplastic syndromes: Association with bone marrow cell apoptosis and peripheral cytopenia
Overexpression of MCM2 in myelodysplastic syndromes: Association with bone marrow cell apoptosis and peripheral cytopenia
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DOI：
10.1016/j.yexmp.2011.11.003
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发表时间：
2012-02-01
影响因子：
3.6
通讯作者：
Kitagawa, Masanobu
中科院分区：
文献类型：
--
作者：
Suzuki, Shiho;Kurata, Morito;Kitagawa, Masanobu
骨髓增生异常综合征(MDS)以骨髓细胞增殖和凋亡为特征。微小染色体维持蛋白(MCM)2在我们最近的研究中被证明具有促凋亡作用，它是调节DNA复制所必需的。因此，为了确定MCM2在MDS中的作用，我们进行了实时定量聚合酶链式反应、免疫组织化学和体外分析。结果显示，MCM2在MDS中的表达显著高于对照组和AML，MCM2与Ki67标记指数(US)无相关性，而MCM2 LLS与caspase3us的表达显著相关。体外分析表明，MCM2过表达可诱导HL60细胞发生凋亡。MDS骨髓中MCM2和裂解caspase 3双阳性细胞比例较高，且与白细胞减少程度相关。这些结果提示，MCM2的表达上调与MDS的频繁细胞凋亡有关，并可能在MDS的发病机制中起重要作用。(C)2011 Elsevier Inc.保留所有权利。
Myelodysplastic syndromes (MDS) are characterized by proliferation and apoptosis of bone marrow cells. Minichromosome maintenance protein (MCM) 2, which is known to be essential for regulating DNA replication, has proven to have a pro-apoptotic effect in our recent study. Thus, to determine the role of MCM2 in MDS, real-time PCR, immunohistochemistry and in vitro analysis were performed. Our results showed higher MCM2 expression in MDS than in control and AML Notably, there was no correlation between MCM2 and Ki67-labeling indices (Us) in MDS, while MCM2 Lls were significantly correlated with cleaved caspase 3 Us in MDS. In vitro analysis revealed that MCM2 overexpression induced apoptosis in HL60 cells. Furthermore, MDS bone marrow exhibited higher ratio of MCM2 and cleaved caspase 3 double-positive cells and the ratio was correlated with the degree of leukocytopenia. These results suggest that the up-regulated expression of MCM2 is associated with frequent apoptosis in MDS and may have an important role in the pathogenesis of MDS. (C) 2011 Elsevier Inc. All rights reserved.