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A Pin1/PML/P53 axis activated by retinoic acid in
- Source :
- Haematologica
- Publication Year :
- 2020
-
Abstract
- 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.
Details
- ISSN :
- 15928721
- Volume :
- 106
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.pmid.dedup....26e0e6d1609749209cbebe451c89a3a5