Lu Jiawen, Xue Xiuhua, Wang Haitao, Hao Ying, Yang Qiong
Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing, China.
National Experimental Teaching Demonstration Center for Life Science and Technology, College of Life Sciences, Beijing Normal University, Beijing, China.
Exp Hematol. 2025 Aug;148:104771. doi: 10.1016/j.exphem.2025.104771. Epub 2025 May 8.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by the accumulation of genomic lesions that affect the development of T cells. Notch1 signaling controls the expression of numerous T-lineage genes, thus playing essential parts in T-cell differentiation. T-ALL can be classified into two subtypes according to the immunophenotypic and genetic makeup: early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and non-ETP-ALL. The relationship between constitutive activation of Notch1 signaling and non-ETP-ALL has been thoroughly studied; however, how Notch1 signaling influences ETP-ALL remains unclear. Targeting Notch1 signaling is a promising treatment for T-ALL, and γ-secretase inhibitors (GSIs), which prevent Notch1 signaling from being activated, show a degree of antineoplastic activity in previous clinical development. But these agents just have satisfactory effects in non-ETP-ALL; further study should be carried out to investigate fitting targeting drugs.
T细胞急性淋巴细胞白血病（T-ALL）是一种侵袭性血液系统恶性肿瘤，由影响T细胞发育的基因组损伤积累所致。Notch1信号通路控制众多T系基因的表达，因此在T细胞分化中起关键作用。根据免疫表型和基因组成，T-ALL可分为两种亚型：早期T细胞前体急性淋巴细胞白血病（ETP-ALL）和非ETP-ALL。Notch1信号通路的组成性激活与非ETP-ALL之间的关系已得到充分研究；然而，Notch1信号通路如何影响ETP-ALL仍不清楚。靶向Notch1信号通路是治疗T-ALL的一种有前景的方法，γ-分泌酶抑制剂（GSIs）可阻止Notch1信号通路被激活，在先前的临床开发中显示出一定程度的抗肿瘤活性。但这些药物仅在非ETP-ALL中有满意疗效；应进一步开展研究以探寻合适的靶向药物。
