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

Journal of chemotherapy (Florence, Italy)(2022)

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摘要
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 , C-MYC and β-catenin in T-ALL cell lines. Then, we indicated that TPL induced the expression of Wnt pathway antagonists, including , , and , 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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关键词
T-cell acute lymphoblastic leukaemia,Wnt antagonists,Wnt signalling pathway,epigenetics,triptolide
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