Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia
Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia
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DOI：
10.1126/science.1102160
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发表时间：
2004-10-08
期刊：
影响因子：
56.9
通讯作者：
Aster, JC
中科院分区：
文献类型：
--
作者：
Weng, AP;Ferrando, AA;Aster, JC
非常罕见的人类 T 细胞急性淋巴细胞白血病 (T-ALL) 病例存在涉及 NOTCH1 的染色体易位，NOTCH1 是一种编码调节正常 T 细胞发育的跨膜受体的基因。在这里，我们报告超过 50% 的人类 T-ALL，包括所有主要分子致癌亚型的肿瘤，都具有涉及 NOTCH1 的细胞外异二聚化结构域和/或 C 端 PEST 结构域的激活突变。这些发现极大地扩展了激活的NOTCH1在人类T-ALL分子发病机制中的作用，并为干扰NOTCH信号传导的靶向治疗提供了强有力的理论依据。
Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.