Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells
Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells
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DOI：
10.1002/path.1454
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发表时间：
2003-11-01
影响因子：
7.3
通讯作者：
Dörken, B
中科院分区：
文献类型：
--
作者：
Emmerich, F;Theurich, S;Dörken, B
霍奇金淋巴瘤（HL）的发病机制尚不清楚。以前的研究已经证明了转录因子NF-κ B（NF-κ B）在Hodgkin/Reed-Sternberg（HRS）细胞中的组成性核活性是保护这些细胞免于凋亡的重要先决条件。作为导致HRS细胞中组成型NF-κ B活性的分子机制，NF-κ B抑制剂I κ B α（I κ B α）的突变最近已在CHL患者的经典（c）HL衍生细胞系中鉴定。在本研究中，NF-κ B抑制剂I κ B抑制剂（I κ B抑制剂）已被分析的体细胞突变，在同一组的6名患者已经研究了I κ B α突变，以及在cHL衍生的细胞系。在一个cHL来源的细胞系（L428）中，发现了一个产生前末端终止密码子的半合子移码突变，导致蛋白质严重截短。此外，在一个患者的HRS细胞中，发现了一个影响IkappaBalpha基因内含子I 5 '剪接位点的半合子突变。这些结果与最近描述的IkappaBalpha突变相结合，表明缺陷型NF-κ B抑制剂出现频率比以前认为的更高，并可能解释在相当大比例的cHL病例中NF-κ B的组成性核活性。版权所有（C）2003约翰威利父子有限公司。
The pathogenesis of Hodgkin lymphoma (HL) is still unclear. Previous investigations have demonstrated constitutive nuclear activity of the transcription factor NF kappa B (NF-kappaB) in Hodgkin/Reed-Sternberg (HRS) cells as an important prerequisite in protecting these cells from apoptosis. As a molecular mechanism leading to constitutive NF-kappaB activity in HRS cells, mutations of the NF-kappaB inhibitor I kappa B alpha (IkappaBalpha) have recently been identified in classical (c) HL-derived cell lines in a patient with CHL. In the present study, the NF-kappaB inhibitor I kappa B epsilon (IkappaBepsilon) has been analysed for somatic mutations in the same group of six patients already studied for IkappaBalpha mutations, as well as in cHL-derived cell lines. In one cHL-derived cell line (L428), a hemizygous frame-shift mutation generating a pre-terminal stop codon resulting in a severely truncated protein was found. Moreover, in the HRS cells of one patient, a hemizygous mutation affecting the 5'-splicing site of intron I of the IkappaBepsilon, gene was found. These results, in combination with recently described IkappaBalpha mutations, indicate that defective NF-kappaB inhibitors appear more frequent than previously thought and might explain the constitutive nuclear activity of NF-kappaB in a significant proportion of cHL cases. Copyright (C) 2003 John Wiley Sons, Ltd.