Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies.
Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies.
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DOI：
10.1002/path.2789
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发表时间：
2011-01
影响因子：
7.3
通讯作者：
Pear, Warren S.
中科院分区：
文献类型：
--
作者：
Aster, Jon C.;Blacklow, Stephen C.;Pear, Warren S.
关键词：
Notch受体参与高度保守的信号通路，以上下文和剂量依赖的方式调节正常发育和组织动态平衡。Notch信号失控与许多疾病有关，但最明显的致病作用的例子是T细胞淋巴母细胞白血病/淋巴瘤(T-LL)，在T细胞淋巴母细胞白血病/淋巴瘤(T-LL)中，大多数人类和小鼠肿瘤获得了导致Notch1信号异常增加的突变。值得注意的是，Notch突变的选择压力似乎在T-LL癌症中几乎是独一无二的，推测反映了Notch在正常T细胞前体细胞中的特殊上下文依赖作用。然而，最近有一些报告表明，Notch信号在其他形式的血液系统恶性肿瘤中也具有微妙而重要的作用。在这里，我们回顾了Notch信号在各种血癌中的作用，重点关注T-LL，着眼于靶向治疗。
Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context- and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling. Remarkably, it appears that the selective pressure for Notch mutations is virtually unique among cancers to T-LL, presumably reflecting a special context-dependent role for Notch in normal T cell progenitors. Nevertheless, there are some recent reports suggesting that Notch signalling has subtle yet important roles in other forms of hematologic malignancy as well. Here, we review the role of Notch signalling in various blood cancers, focusing on T-LL with an eye toward targeted therapeutics.
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