SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia
SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia
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DOI：
10.1182/blood-2012-05-428938
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发表时间：
2013-01-03
期刊：
影响因子：
20.3
通讯作者：
Mueschen, Markus
中科院分区：
文献类型：
--
作者：
Ramezani-Rad, Parham;Geng, Huimin;Mueschen, Markus
Sox4转录因子介导早期b细胞分化。与正常前b细胞相比，Ph+ ALL细胞中SOX4启动子区显著低甲基化。功能缺失和功能获得实验发现Sox4是ALL细胞中PI3K/AKT和MAPK信号的关键激活因子。ChIP实验证实，SOX4结合并转录激活PI3K/AKT和MAPK信号通路中多个组分的启动子。cre介导的Sox4缺失对正常的前b细胞几乎没有影响，但会损害白血病细胞的增殖和活力，这是由BCL2L1和组成性活性AKT和p110 PI3K拯救的。与这些发现一致，在一项儿科临床试验中，诊断时ALL细胞中SOX4的高水平表达预示着不良预后（COG P9906）。总的来说，这些研究确定SOX4是ALL中致癌PI3K/AKT和MAPK信号传导的中心介质。[j] .血液，2013;121(1):148-155。
The Sox4 transcription factor mediates early B-cell differentiation. Compared with normal pre-B cells, SOX4 promoter regions in Ph+ ALL cells are significantly hypomethylated. Loss and gain-of-function experiments identified Sox4 as a critical activator of PI3K/AKT and MAPK signaling in ALL cells. ChIP experiments confirmed that SOX4 binds to and transcriptionally activates promoters of multiple components within the PI3K/AKT and MAPK signaling pathways. Cre-mediated deletion of Sox4 had little effect on normal pre-B cells but compromised proliferation and viability of leukemia cells, which was rescued by BCL2L1 and constitutively active AKT and p110 PI3K. Consistent with these findings, high levels of SOX4 expression in ALL cells at the time of diagnosis predicted poor outcome in a pediatric clinical trial (COG P9906). Collectively, these studies identify SOX4 as a central mediator of oncogenic PI3K/AKT and MAPK signaling in ALL. (Blood. 2013; 121(1): 148-155)