下调和上调
癌症研究
细胞生长
白血病
细胞周期
调节器
癌基因
祖细胞
信号转导
生物
细胞生物学
细胞
基因
干细胞
免疫学
遗传学
作者
Marta Sánchez-Martín,Adolfo A. Ferrando
出处
期刊:Blood
[American Society of Hematology]
日期:2017-01-23
卷期号:129 (9): 1124-1133
被引量:212
标识
DOI:10.1182/blood-2016-09-692582
摘要
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a highly proliferative hematologic malignancy that results from the transformation of immature T-cell progenitors. Aberrant cell growth and proliferation in T-ALL lymphoblasts are sustained by activation of strong oncogenic drivers promoting cell anabolism and cell cycle progression. Oncogenic NOTCH signaling, which is activated in more than 65% of T-ALL patients by activating mutations in the NOTCH1 gene, has emerged as a major regulator of leukemia cell growth and metabolism. T-ALL NOTCH1 mutations result in ligand-independent and sustained NOTCH1-receptor signaling, which translates into activation of a broad transcriptional program dominated by upregulation of genes involved in anabolic pathways. Among these, the MYC oncogene plays a major role in NOTCH1-induced transformation. As result, the oncogenic activity of NOTCH1 in T-ALL is strictly dependent on MYC upregulation, which makes the NOTCH1-MYC regulatory circuit an attractive therapeutic target for the treatment of T-ALL.
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