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| Home > Publications database > The NOTCH1 and miR-34a signaling network is affected by TP53 alterations in CLL. |
| Home > Publications database > The NOTCH1 and miR-34a signaling network is affected by TP53 alterations in CLL. |
| Journal Article | DKFZ-2024-01685 |
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2024
Taylor & Francis Group
London [u.a.]
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Please use a persistent id in citations: doi:10.1080/10428194.2024.2392839
Abstract: In chronic lymphocytic leukemia (CLL), TP53 mutations or deletions on chromosome 17p lead to adverse prognosis and reduced levels of miR-34a, which targets NOTCH1. Also, hyperactivated NOTCH1 signaling is crucial for CLL progression. Here we explored the interaction between p53, miR-34a, and NOTCH1 in CLL. We investigated the effect of p53 and miR-34a on NOTCH1 signaling and expression in CLL cells with altered TP53. Our results indicate that miR-34a reduces NOTCH1 3' UTR activity but might not be a mediator between p53 signaling and NOTCH1. p53 activation increases miR-34a expression and NOTCH1 protein levels, correlating with decreased NOTCH1 and miR-34a levels in primary CLL cells with TP53 alterations. Some samples with high NOTCH1 levels presented increased BCL-2, suggesting an anti-apoptotic mechanism of a potentially direct p53-NOTCH1 relation in CLL. This study deepens the understanding of the p53-miR-34a-NOTCH1 signaling network, providing insights that could guide future therapeutic strategies for CLL.
Keyword(s): CLL ; NOTCH1 ; miR-34a ; p53 ; signaling network
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