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Triptolide inhibits T-cell acute lymphoblastic leukaemia by affecting aberrant epigenetic events in the Wnt signalling pathway

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单位: [1]Fudan Univ, Jinshan Hosp, Ctr Tumor Diag & Therapy, Shanghai, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Hematol, Wuhan, Hubei, Peoples R China
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关键词: Wnt signalling pathway T-cell acute lymphoblastic leukaemia Wnt antagonists triptolide epigenetics

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T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematologic disease that accounts for 15% of childhood and 25% of adult ALL cases. Triptolide (TPL) is an active component of Tripterygium wilfordii and was recently discovered to suppress the growth of some cancers, including ALL, but the underlying mechanism has yet to be elucidated. Dysfunction of the Wnt signalling pathway has been reported to be an important event in the pathogenesis of T-ALL. In this study, we investigated the effects of TPL on the Wnt pathway and found that it suppressed the expression of TCF7, C-MYC and beta-catenin in T-ALL cell lines. Then, we indicated that TPL induced the expression of Wnt pathway antagonists, including WIF1, SOX17, CDH1 and SFRP5, in T-ALL cells. Further analysis indicated that TPL induced the demethylation of these genes, which may be related to the inhibited expression of methyltransferases DNMT1 and DNMT3a. In conclusion, our results suggest that TPL inhibits T-ALL by inhibiting aberrant epigenetic events in dysregulated Wnt signalling.

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出版当年[2022]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 药学 4 区 传染病学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 传染病学 4 区 肿瘤学 4 区 药学
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出版当年[2021]版:
Q4 INFECTIOUS DISEASES Q4 ONCOLOGY Q4 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q3 INFECTIOUS DISEASES Q3 ONCOLOGY Q3 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者单位: [1]Fudan Univ, Jinshan Hosp, Ctr Tumor Diag & Therapy, Shanghai, Peoples R China
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