摘要
Notch信号通路由Notch受体、配体和胞内的效应分子组成。1991年,第1个人类Notch家族成员Notch1基因在具有t(7;9)(q34;q34.3)染色体易位的急性T淋巴细胞白血病中发现,由此揭示了Notch信号通路是一条影响细胞命运的保守而重要的信号通路,几乎涉及所有细胞的增殖、分化和凋亡。与此同时,Notch信号通路在恶性血液病和实体瘤的形成和发展中所起的作用也日趋清晰。在超过半数的急性T淋巴细胞白血病中发现了突变型Notch1基因,但其作为原发还是继发仍不确定。近年来的研究发现,Notch信号通路具有致癌和抑癌双重作用。现就Notch信号通路在不同类型恶性血液病发生和发展中所起的作用、急性T淋巴细胞白血病中突变型Notch1基因类型、Notch信号通路与其它相关信号通路的关系及Notch信号通路抑制剂在恶性血液病治疗中的作用等相关研究进展进行综述。
Notch signaling pathway consists of three parts： Notch receptor,Notch ligand and intracellular effector.Notch is a family of transmembrane proteins that function both as cell surface receptors and transcription regulators.As the first human gene of this family,Notch1 was discovered in 1991 through the analysis of the chromosomal translocation t（7;9）（q34;q34.3） observed in patients with T-cell acute lymphoblastic leukemia（T-ALL）.Since then Notch signaling has been implicated in multiple processes that govern normal morphogenesis,differentiation,cell proliferation and apoptosis.At the same time a role of Notch in the pathogenesis of hematologic and solid malignancies has become apparent.The identification of activating mutations in Notch1 were discovered in over 50% of T-ALL patients.However,whether the mutation in Notch1 is an early event or an secondary event is still unknown.It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive.This review focuses on the recent findings regarding the Notch signaling during the development and progression of different kinds of hematologic malignancies,the types of mutations in Notch1 in T-ALL and the relationship between Notch signaling pathway and other signaling pathways.In addition,the clinical prospects of Notch inhibitors also are discussed.
出处
《中国实验血液学杂志》
CAS
CSCD
2011年第6期1550-1555,共6页
Journal of Experimental Hematology
基金
国家自然科学基金(编号30971285)
高等学校博士学科点专项科研基金(编号200800620004)
天津医科大学重点学科基金(编号2009xk50)
