Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia

被引：2195

作者：

Weng, AP

Ferrando, AA

Lee, W

Morris, JP

Silverman, LB

Sanchez-Irizarry, C

Blacklow, SC

Look, AT

Aster, JC ^{[1
]}

机构：

[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA

[2] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA

来源：

SCIENCE | 2004年 / 306卷 / 5694期

关键词：

D O I：

10.1126/science.1102160

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

收藏

页码：269 / 271

页数：3

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