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The NOTCH1 and miR-34a signaling network is affected by TP53 alterations in CLL.
Ehrmann, Alena Sophie; Zadro, Alex; Tausch, Eugen; Schneider, Christof; Stilgenbauer, Stephan; Mertens, Daniel.
Afiliación
  • Ehrmann AS; Division of CLL, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
  • Zadro A; Mechanisms of Leukemogenesis (B061), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Tausch E; Division of CLL, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
  • Schneider C; Division of CLL, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
  • Stilgenbauer S; Comprehensive Cancer Center Ulm (CCCU), University Hospital of Ulm, Ulm, Germany.
  • Mertens D; Division of CLL, Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
Leuk Lymphoma ; : 1-13, 2024 Aug 19.
Article en En | MEDLINE | ID: mdl-39161195
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leuk Lymphoma Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Leuk Lymphoma Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos