Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells

Author:

El Hajj Hiba12,Dassouki Zeina13,Berthier Caroline4,Raffoux Emmanuel5,Ades Lionel67,Legrand Olivier8910,Hleihel Rita13,Sahin Umut4,Tawil Nadim12,Salameh Ala12,Zibara Kazem11,Darwiche Nadine12,Mohty Mohamad8910,Dombret Hervé5,Fenaux Pierre67,de Thé Hugues4,Bazarbachi Ali13

Affiliation:

1. Department of Internal Medicine,

2. Department of Experimental Pathology, Microbiology and Immunology, and

3. Department of Cell Biology, Anatomy and Physiological Sciences, American University of Beirut, Beirut, Lebanon;

4. INSERM/Centre National de la Recherche Scientifique/University Paris Diderot, Unités Mixtes de Recherche 944/7212, Collège de France and Equipe labellisée Ligue contre le Cancer,

5. Service d’Hématologie Clinique, and

6. Service d’Hématologie Senior, Hôpital St. Louis, Paris, France;

7. Service d’Hématologie Clinique, Hôpital Avicenne, Bobigny, France;

8. INSERM U938, and

9. Service d’Hématologie, Hôpital St. Antoine, Paris, France;

10. Université Pierre et Marie Curie, Paris, France;

11. ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, Lebanese University, Beirut, Lebanon; and

12. Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon

Abstract

Key Points RA/arsenic induces proteasomal degradation of mutant NPM1, yielding AML growth arrest and apoptosis. RA/arsenic treatment restored nucleolar localization of NPM1 and significantly reduced bone marrow blasts in NPM1 mutant AML patients.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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