Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2021

Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Marie Sabatier
Emeline Boet
  • Fonction : Auteur
Sonia Zaghdoudi
  • Fonction : Auteur
Nathan Guiraud
  • Fonction : Auteur
Alexis Hucteau
Nathaniel Polley
  • Fonction : Auteur
Guillaume Cognet
Estelle Saland
  • Fonction : Auteur
Laura Lauture
  • Fonction : Auteur
Thomas Farge
  • Fonction : Auteur
Ambrine Sahal
  • Fonction : Auteur
Vera Pancaldi
Sarah Bertoli
  • Fonction : Auteur
Pierre Bories
Christian Récher
Héléna Boutzen
  • Fonction : Auteur
Véronique Mansat-de Mas
Lucille Stuani
Jean-Emmanuel Sarry

Résumé

Relapses and resistance to therapeutic agents are major barriers in the treatment of acute myeloid leukemia (AML) patients. These unfavorable outcomes emphasize the need for new strategies targeting drug-resistant cells. As IDH mutations are present in the preleukemic stem cells and systematically conserved at relapse, targeting IDH mutant cells could be essential to achieve a long-term remission in the IDH mutant AML subgroup. Here, using a panel of human AML cell lines and primary AML patient specimens harboring IDH mutations, we showed that the production of an oncometabolite (R)-2-HG by IDH mutant enzymes induces vitamin D receptor-related transcriptional changes, priming these AML cells to differentiate with pharmacological doses of ATRA and/or VD. This activation occurs in a CEBPα-dependent manner. Accordingly, our findings illuminate potent and cooperative effects of IDH mutations and the vitamin D receptor pathway on differentiation in AML, revealing a novel therapeutic approach easily transferable/immediately applicable to this subgroup of AML patients.

Dates et versions

hal-04415805 , version 1 (24-01-2024)

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Citer

Marie Sabatier, Emeline Boet, Sonia Zaghdoudi, Nathan Guiraud, Alexis Hucteau, et al.. Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations. Cancers, 2021, 13 (20), pp.5243. ⟨10.3390/cancers13205243⟩. ⟨hal-04415805⟩
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