A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolys...

Descripción completa

Detalles Bibliográficos
Autores principales: Hleihel, Rita, El Hajj, Hiba, Wu, Hsin-Chieh, Berthier, Caroline, Zhu, Hong-Hu, Massoud, Radwan, Chakhachiro, Zaher, El Sabban, Marwan, de The, Hugues, Bazarbachi, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634200/
https://www.ncbi.nlm.nih.gov/pubmed/34047175
http://dx.doi.org/10.3324/haematol.2020.274878
Descripción
Sumario:Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.

Ejemplares similares