Notch signaling in leukemia
Notch signaling in leukemia
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DOI：
10.1097/00062752-200107000-00010
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发表时间：
2001-07-01
影响因子：
3.2
通讯作者：
Pear, WS
中科院分区：
文献类型：
--
作者：
Aster, JC;Pear, WS
哺乳动物Notch同源物首次从Notch I参与人类t细胞白血病亚群的复发性染色体易位中确定。易位的效果是双重的：Notch表达被置于t细胞特异性元件的控制之下，Notch被截断，产生一个组成活性蛋白。随后的研究表明Notch1是T细胞承诺所必需的，并且仅对T细胞具有嗜瘤性。在过去的一年中，一些小鼠模型被用来解剖Notch信号在淋巴细胞发育和白血病中的功能。这些模型表明Notch1驱动T细胞承诺的最早阶段，并且Notch信号必须在双阳性阶段下调，才能发生适当的T细胞发育。Notch1、Notch2或Notch3介导的构成型Notch信号通路易致t细胞白血病。未来的研究有望阐明Notch导致转化的机制。鉴定Notch信号的转录靶标可能会产生重要的见解。(C) 2001 Lippincott Williams & Wilkins公司
Mammalian Notch homologs were first identified from the involvement of Notch I in a recurrent chromosomal translocation in a subset of human T-cell leukemias. The effect of the translocation was twofold: Notch expression was placed under the control of a T-cell-specific element, and Notch was truncated, resulting in a constitutively active protein. Subsequent work has shown that Notch1 is required for T cell commitment and is exclusively oncotropic for T cells. During the past year, several murine models have been used to dissect the function of Notch signaling in lymphoid development and leukemia. These models show that Notch1 drives the earliest stages of T cell commitment and that Notch signaling must be downregulated by the double positive stage for proper T cell development to occur. Constitutive Notch signaling mediated by Notch1, Notch2, or Notch3 predisposes to T-cell leukemia. Future studies are expected to elucidate the mechanisms by which Notch leads to transformation. Identification of the transcriptional targets of Notch signaling is likely to yield important insights. (C) 2001 Lippincott Williams & Wilkins, Inc.