[生存素在儿童急性白血病骨髓细胞中的表达及其定位：与治疗效果的关系]
[Expression of survivin and its location in bone marrow cells of childhood acute leukemia: relationship to therapeutic efficacy].
作者信息
Hou Yan, Hu Qun, Liu Ai-Guo, Zhang Liu-Qing, Liu Shuang-You
机构信息
Research Laboratory of Pediatric Hematology, Tongji Hosipital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
出版信息
Zhongguo Dang Dai Er Ke Za Zhi. 2006 Apr;8(2):101-4.
OBJECTIVE
Survivin, a unique member of the inhibitor of apoptosis protein (IAP) family, plays an important role in regulating both apoptosis and cell division. Overexpression of survivin is associated with increased risk of recurrence and poor outcome in cancer patients. This study aimed to investigate the expression of survivin and its location as well as the relationship between cellular location and expression of survivin and the therapeutic efficacy at the cellular level.
METHODS
The expression of survivin protein was detected by immunohistochemical assay in bone marrow cells from 62 children with acute leukemia and 40 hospitalized children who did not have leukemia (Control group), and in a human acute T lymphocytic leukemia cell line (Molt-4 cells) treated in vitro with daunorubicin (DNR). Cell apoptosis was detected using flow cytometry.
RESULTS
Survivin protein was expressed in 41.9% of the 62 children with acute leukemia but in only 5.0% of the Control group (chi(2)=16.66; P < 0.01). The expression rate of survivin was 46.2% in cytoplasm and 53.9% in nucleus in the children with acute leukemia (chi(2)0.3077; P> 0.05). However, the remission rate of patients in whom survivin expression was seen in the nucleus was significantly higher than that in patients in whom survivin was expressed in cytoplasm after chemotherapy. The survivin expression in Molt-4 cells decreased remarkably by DNR treatment in a time and dosage-dependent manner. DNR treatment also induced survivin transllocation from cytoplasm to nucleus and cell apoptosis in a time and dosage-dependent manner.
CONCLUSIONS
Survivin may play an important role in the development and prognosis of childhood acute leukemia. The different expression pattern of survivin in the cytoplasm and the nucleus may be associated with therapeutic efficacy and prognosis in acute leukemia. DNR may reduce the survivin expression in leukemic cells and induce cell apoptosis.
目的
生存素是凋亡抑制蛋白（IAP）家族的一个独特成员，在调节细胞凋亡和细胞分裂中起重要作用。生存素的过表达与癌症患者复发风险增加及预后不良相关。本研究旨在探讨生存素的表达及其定位，以及生存素的细胞定位与表达之间的关系和细胞水平上的治疗效果。
方法
采用免疫组织化学法检测62例急性白血病患儿和40例非白血病住院患儿（对照组）骨髓细胞中生存素蛋白的表达，并检测体外经柔红霉素（DNR）处理的人急性T淋巴细胞白血病细胞系（Molt-4细胞）中生存素蛋白的表达。采用流式细胞术检测细胞凋亡。
结果
62例急性白血病患儿中41.9%表达生存素蛋白，而对照组仅5.0%表达（χ²=16.66；P<0.01）。急性白血病患儿中生存素在细胞质中的表达率为46.2%，在细胞核中的表达率为53.9%（χ²=0.3077；P>0.05）。然而，化疗后细胞核中出现生存素表达的患者缓解率明显高于细胞质中表达生存素的患者。DNR处理使Molt-4细胞中生存素表达明显降低，呈时间和剂量依赖性。DNR处理还使生存素从细胞质转位至细胞核，并诱导细胞凋亡，呈时间和剂量依赖性。
结论
生存素可能在儿童急性白血病的发生发展及预后中起重要作用。生存素在细胞质和细胞核中的不同表达模式可能与急性白血病的治疗效果和预后相关。DNR可能降低白血病细胞中生存素的表达并诱导细胞凋亡。
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