...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia
【24h】

Expression of dominant-negative and mutant isoforms of the antileukemic transcription factor Ikaros in infant acute lymphoblastic leukemia

机译：抗白血病转录因子Ikaros的显性负突变型在婴儿急性淋巴细胞白血病中的表达

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Ikaros, a zinc finger-containing DNA-binding protein, is required for normal lymphocyte development, and germline mutant mice that express only non-DNA binding dom- inant-negative "leukemogenic" Ikaros isoforms lacking critical N-terminal zinc fingers develop an aggressive form of lympho- blastic leukemia 3-6 months after birth. Therefore, we sought to determine whether molecular abnormalities involving the Ikaros gene could contribute to the development of acute lymphoblastic leukemia (ALL) in infants. Primary leukemic cells were freshly obtained from 12 infants (< 1 year of age) with newly diagnosed ALL. In leukemic cells from each of the 12 infants with ALL, we found high level expression of dominant-negative isoforms of Ikaros with abnormal subcellular compartmentalization pat- terns. PCR cloning and nucleotide sequencing were used to identify the specific Ikaros isoforms and detect Ikaros gene mutations in these cells. Leukemic cells from seven of seven infants with ALL, including five of five MLL-AF4~+ infants, expressed dominant-negative Ikaros isoforms Ik-4, Ik-7, and Ik-8 that lack critical N-terminal zinc fingers. In six of seven patients, we detected a specific mutation leading to an in-frame deletion of 10 amino acids (#DELTA3 KSSMPQKFLG) upstream of the tran- scription activation domain adjacent to the C-terminal zinc fingers of Ik-2, Ik-4, Ik-7, and Ik-8. In contrast, only wild-type Ik-1 and Ik-2 isoforms with normal nuclear localization were found in normal infant bone marrow cells and infant thymocytes. These results implicate the expression of dominant-nega
机译：Ikaros是含锌指的DNA结合蛋白，是正常淋巴细胞发育所必需的，而只表达非DNA结合显性负性“致白血病” Ikaros亚型且缺乏关键的N末端锌指的种系突变小鼠会产生攻击性出生后3-6个月的淋巴母细胞白血病形式。因此，我们试图确定涉及Ikaros基因的分子异常是否可能导致婴儿急性淋巴细胞白血病（ALL）的发展。原发性白血病细胞是从新诊断为ALL的12例婴儿（<1岁）中新鲜获得的。在12例ALL患儿的每例白血病细胞中，我们发现Ikaros的显性负亚型具有异常的亚细胞区室化模式。 PCR克隆和核苷酸测序用于鉴定特定的Ikaros同工型并检测这些细胞中的Ikaros基因突变。来自七个ALL婴儿中的七个的白血病细胞，包括五个MLL-AF4〜+婴儿中的五个，表达了显性阴性的Ikaros亚型Ik-4，Ik-7和Ik-8，这些亚型缺少关键的N末端锌指。在七名患者中的六名中，我们检测到一个特定的突变，导致转录激活域上游与Ik-2，Ik-C的C末端锌指相邻的10个氨基酸（＃DELTA3 KSSMPQKFLG）框内缺失。 4，Ik-7和Ik-8。相反，在正常婴儿骨髓细胞和婴儿胸腺细胞中仅发现具有正常核定位的野生型Ik-1和Ik-2同工型。这些结果暗示显性负性的表达

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号