A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia.
Haematologica
; 106(12): 3090-3099, 2021 12 01.
Article
in En
| MEDLINE
| ID: mdl-34047175
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
/
Leukemia, Promyelocytic, Acute
Limits:
Humans
Language:
En
Journal:
Haematologica
Year:
2021
Type:
Article
Affiliation country:
Lebanon