南京医科大学学报（自然科学版）2025，Vol.45Issue(9)：1258-1266,1285,10.DOI:10.7655/NYDXBNSN250487
NOTCH1信号通路与T细胞急性淋巴细胞白血病的研究进展
Research advances in the NOTCH1 signaling pathway and T-cell acute lymphoblastic leukemia
摘要
Abstract
T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive hematologic malignancy,accounting for approximately 15%and 25%of all pediatric and adult ALL cases,respectively.In T-ALL,approximately 60%of cases have NOTCH1 mutations.These mutations,caused by truncation of the PEST(a cluster of proline,glutamic acid,serine,and threonine residues)domain or abnormal heterodimerization,lead to impaired degradation or persistent release of the NOTCH intracellular domain(NICD),resulting in aberrant activation of downstream target genes such as MYC.This process synergizes with oncogenic factors like TAL1 and LMO2 to drive leukemogenesis.Among therapeutic strategies targeting NOTCH1,γ-secretase inhibitors have been limited by their broad-spectrum toxicity.However,novel agents such as the PSEN1-selective inhibitor MRK-560,NOTCH1 monoclonal antibody(OMP-52M51),and the small molecule CB-103 demonstrate precise inhibition of NOTCH1 signaling with reduced toxicity.Additionally,metabolic interventions and epigenetic regulation have shown synergistic potential.Although significant progress has been made in understanding the role of the NOTCH1 signaling pathway in T-ALL,further research is needed to unravel its complexities.This review focuses on the impact of NOTCH1 mutations on T-ALL cells,discusses drugs targeting the NOTCH1 pathway,and explores the association between NOTCH1 signaling and drug resistance.关键词
NOTCH1信号通路/T-ALL/靶向治疗Key words
NOTCH1 signaling pathway/T-ALL/targeted therapy分类
医药卫生引用本文复制引用
陈奕孜,翁昌健,陆超..NOTCH1信号通路与T细胞急性淋巴细胞白血病的研究进展[J].南京医科大学学报（自然科学版）,2025,45(9):1258-1266,1285,10.基金项目
国家自然科学基金(81770162) （81770162）
