Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia
Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia
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DOI：
10.1016/j.leukres.2004.05.013
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发表时间：
2005-01-01
影响因子：
2.7
通讯作者：
Anderson, KP
中科院分区：
文献类型：
--
作者：
Hammond, SM;Crable, SC;Anderson, KP
LMO 2的异位表达发生在大约45%的T系急性淋巴细胞白血病（T-ALL）中，有时与染色体易位有关。最近，在一项基因治疗试验中，由于通过整合逆转录病毒载体激活LMO 2，两名参与者发生了淋巴增生性疾病。为了研究这些调控中断，我们分析了启动子区域，并确定了组织特异性阻遏物。含有该元件的片段也可以产生组织特异性抑制SV 40启动子的转录。这种抑制涉及组蛋白乙酰化，其可以用曲古抑菌素A（TSA）缓解。阴性元件位于已知染色体易位中始终从LMO 2移除的区域中。(C)2004爱思唯尔有限公司保留所有权利。
Ectopic expression of LMO2 occurs in approximately 45% of T-lineage acute lymphoblastic leukemias (T-ALL), sometimes in association with chromosomal translocations. Recently, a lymphoproliferative disorder developed in two participants in a gene therapy trial due to LMO2 activation via integration of the retroviral vector. To investigate these regulatory disruptions, we analyzed the promoter region and identified a tissue-specific repressor. The fragment containing this element could also produce tissue-specific suppression of transcription from the SV40 promoter. This suppression involves histone acetylation which can be relieved with Trichostatin A (TSA). The negative element is in a region consistently removed from LMO2 in the known chromosomal translocations. (C) 2004 Elsevier Ltd. All rights reserved.