Haematologica (Roma), 2021-12, Vol.106 (12), p.3090-3099
2021
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- Autor(en) / Beteiligte
- Titel
- A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia
- Ist Teil von
- Haematologica (Roma), 2021-12, Vol.106 (12), p.3090-3099
- Ort / Verlag
- Italy
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0390-6078eISSN: 1592-8721DOI: 10.3324/haematol.2020.274878Titel-ID: cdi_pubmed_primary_34047175
- Format
- –
- Schlagworte
- Humans, Leukemia, Myeloid, Acute - drug therapy, Leukemia, Myeloid, Acute - genetics, Leukemia, Promyelocytic, Acute - drug therapy, Leukemia, Promyelocytic, Acute - genetics, Leukemia, Promyelocytic, Acute - metabolism, NIMA-Interacting Peptidylprolyl Isomerase - genetics, NIMA-Interacting Peptidylprolyl Isomerase - metabolism, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Oncogene Proteins, Fusion - metabolism, Tretinoin - pharmacology, Tretinoin - therapeutic use, Tumor Suppressor Protein p53 - genetics