Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia
Differential expression of survivin in bone marrow cells from patients with acute lymphocytic leukemia and chronic lymphocytic leukemia
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DOI：
10.1016/j.leukres.2003.10.013
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发表时间：
2004-05-01
影响因子：
2.7
通讯作者：
Kitagawa, M
中科院分区：
文献类型：
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作者：
Nakagawa, Y;Yamaguchi, S;Kitagawa, M
Survivin是凋亡抑制蛋白（inhibitor of apoptosis protein，IAP）基因家族的成员，广泛存在于胎儿组织和多种人类恶性肿瘤中。本研究采用实时荧光定量RT-PCR和免疫组化方法检测了急性淋巴细胞白血病（ALL）、慢性淋巴细胞白血病（CLL）和对照组骨髓标本中IAP家族蛋白的表达。与对照组相比，CLL骨髓细胞中survivin和cIAP 2 mRNA的表达显著增高（P < 0.05）。免疫组化显示，对照组骨髓中少数散在的髓样细胞中检测到生存素。在ALL骨髓中，超过一半的病例（13例中有8例）显示Survivin阳性表达，而大多数CLL病例（21例中有20例）显示Survivin强表达。Survivin在ALL和CLL中的亚细胞定位差异明显。ALL细胞基本上揭示了生存素的核定位以及在某些情况下的细胞质信号，而CLL细胞从大多数情况下主要表现为胞质表达。然后，进行RT-PCR以检测生存素及其剪接变体生存素-2B和生存素-DeltaEx 3在ALL和CLL细胞中的表达，因为这些变体的分布将受核/胞质转运系统的调节。在ALL和CLL骨髓样本中，野生型生存素的表达比生存素-2B或生存素-DeltaEx 3的表达更显著，尽管生存素-DeltaEx 3的表达在来自生存素表达ALL病例的样本中显著。因此，在ALL和CLL细胞中，生存素mRNA的剪接可能受到不同的调节，从而导致生存素蛋白的核/胞质转运的不同方式。总之，我们的观察表明IAP家族蛋白在ALL和CLL细胞中表达的差异调节机制，尽管IAP家族的功能和Survivin的核/胞质转运机制应在未来的研究中阐明。(C)2003爱思唯尔有限公司。保留所有权利。
Survivin, a member of the inhibitor of apoptosis protein (IAP) gene family, has been detected widely in fetal tissue and in a variety of human malignancies. In the current study, we investigated the expression of IAP family proteins in bone marrow samples from acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL) and control cases by quantitative real-time RT-PCR method and an immunohistochemical approach. Overexpression of survivin and cIAP2 mRNA was significant in CLL bone marrow cells (P < 0.05, respectively) compared with control samples. By immunohistochemistry, survivin was detected in a few scattered myeloid cells in all cases of control bone marrow. Concerning the ALL bone marrow, more than half the cases demonstrated positive expression of survivin (8 out of 13), while the majority of CLL cases (20 out of 21) exhibited intense expression of survivin. The differential subcellular localization of survivin was distinct between ALL and CLL cases. ALL cells essentially revealed nuclear localization of survivin as well as cytoplasmic signals in some cases, while CLL cells from the majority of cases predominantly showed cytoplasmic expression. Next, RT-PCR was performed for the expression of survivin and its splicing variant, survivin-2B and survivin-DeltaEx3 in ALL and CLL cells, as the distribution of these variants would be regulated by nuclear/cytoplasmic transport system. In both ALL and CLL bone marrow samples, the expression of wild-type survivin was more predominant than that of survivin-2B or survivin-DeltaEx3, although the expression of survivin-DeltaEx3 was prominent in samples from survivin-expressing ALL cases. Thus, the splicing of survivin mRNA may be differently regulated in ALL and CLL cells, causing distinct manners of nuclear/cytoplasmic transport of survivin protein. In conclusion, our observations indicate a differential regulatory mechanism for the expression of IAP family proteins in ALL and CLL cells, although the functions of IAP families and the mechanisms of nuclear/cytoplasmic transport of survivin should be clarified in future studies. (C) 2003 Elsevier Ltd. All rights reserved.