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A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia.
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.
Affiliation
  • Hleihel R; Department of Internal Medicine, American University of Beirut, Beirut, Lebanon; Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon.
  • El Hajj H; Department of Experimental Pathology, Microbiology and Immunology, Beirut.
  • Wu HC; Université de Paris, INSERM UMR 944, CNRS UMR 7212, Equipe labellisée par la Ligue Nationale contre le Cancer, IRSL, Hôpital St. Louis, Paris, College de France, PSL University, CIRB, INSERM UMR 1050, CNRS UMR 7241, Paris.
  • Berthier C; Université de Paris, INSERM UMR 944, CNRS UMR 7212, Equipe labellisée par la Ligue Nationale contre le Cancer, IRSL, Hôpital St. Louis, Paris; College de France, PSL University, CIRB, INSERM UMR 1050, CNRS UMR 7241, Paris.
  • Zhu HH; Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou.
  • Massoud R; Department of Internal Medicine, American University of Beirut, Beirut.
  • Chakhachiro Z; Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut.
  • El Sabban M; Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut.
  • De The H; Université de Paris, INSERM UMR 944, CNRS UMR 7212, Equipe labellisée par la Ligue Nationale contre le Cancer, IRSL, Hôpital St. Louis, Paris; College de France, PSL University, CIRB, INSERM UMR 1050, CNRS UMR 7241, Paris.
  • Bazarbachi A; Department of Internal Medicine, American University of Beirut, Beirut; Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut. bazarbac@aub.edu.lb.
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.
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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
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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