Promotion and maintenance of leukemia by ERG
Promotion and maintenance of leukemia by ERG
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DOI：
10.1182/blood-2010-11-320515
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发表时间：
2011-04-07
期刊：
影响因子：
20.3
通讯作者：
Seto, Masao
中科院分区：
文献类型：
--
作者：
Tsuzuki, Shinobu;Taguchi, Osamu;Seto, Masao
Ets相关基因（ERG）位于人类21号染色体上，编码一种转录因子，被认为与儿童期唐氏综合征相关的急性巨核细胞白血病有因果关系。然而，在临床成人白血病中，ERG表达增加指示T细胞急性淋巴细胞白血病和细胞遗传学正常的急性髓性白血病的预后不良，尽管ERG参与成人白血病的发展仍然难以捉摸。在这里，我们表明，在成年骨髓细胞中的ERG的强制表达改变分化，诱导T细胞和红系细胞的扩增，并在小鼠骨髓移植模型中增加髓系祖细胞的频率。扩增的T细胞在获得Notch 1基因突变后发展为T细胞急性淋巴细胞白血病。ERG在B细胞中的靶向表达也改变了前体B细胞的分化并促进其生长。总体而言，这些发现表明ERG在促进各种谱系中的成体造血细胞生长中的一般作用。与此一致，shRNA介导的ERG表达沉默减弱了各种谱系的人白血病细胞系的生长。因此，ERG能够促进白血病的发展，并对其维持至关重要。（血。2011;117（14）：3858-3868）
The Ets-related gene (ERG) located on human chromosome 21 encodes a transcription factor and is thought to be causally related to Down syndrome-associated acute megakaryocytic leukemia in childhood. In clinical adult leukemia, however, increased expression of ERG is indicative of poor prognosis in T-cell acute lymphoblastic leukemia and cytogenetically normal acute myeloid leukemia, although the involvement of ERG in the development of adult leukemia remains elusive. Here, we show that forced expression of ERG in adult BM cells alters differentiation and induces expansion of T and erythroid cells and increases frequencies of myeloid progenitors in mouse BM transplantation models. The expanded T cells then develop T-cell acute lymphoblastic leukemia after acquisition of mutations in the Notch1 gene. Targeted expression of ERG into B cells also altered differentiation and promoted growth of precursor B cells. Overall, these findings suggest a general role of ERG in promoting growth of adult hematopoietic cells in various lineages. In line with this, shRNA-mediated silencing of ERG expression attenuated growth of human leukemia cell lines of various lineages. Thus, ERG is capable of promoting the development of leukemia and is crucial for its maintenance. (Blood. 2011;117(14):3858-3868)