Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2019

Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation

Diana Vara-Ciruelos
  • Fonction : Auteur
Madhumita Dandapani
  • Fonction : Auteur
Fiona Russell
  • Fonction : Auteur
Katarzyna Grzes
  • Fonction : Auteur
Abdelmadjid Atrih
  • Fonction : Auteur
  • PersonId : 789590
  • IdRef : 188119221
Marc Foretz
Benoit Viollet
Douglas Lamont
  • Fonction : Auteur
Doreen Cantrell
  • Fonction : Auteur
  • PersonId : 881073
D Grahame Hardie
  • Fonction : Auteur
D. Grahame Hardie
  • Fonction : Auteur
  • PersonId : 870335

Résumé

AMPK acts downstream of the tumor suppressor LKB1, yet its role in cancer has been controversial. AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk. However, whether this is mediated by cell-autonomous AMPK activation within tumor progenitor cells has been unclear. We report that T-cell-specific loss of AMPK-α1 caused accelerated growth of T cell acute lymphoblastic leukemia/lymphoma (T-ALL) induced by PTEN loss in thymic T cell progenitors. Oral administration of phenformin, but not metformin, delayed onset and growth of lymphomas, but only when T cells expressed AMPK-α1. This differential effect of biguanides correlated with detection of phenformin, but not metformin, in thymus. Phenformin also enhanced apoptosis in T-ALL cells both in vivo and in vitro. Thus, AMPK-α1 can be a cell-autonomous tumor suppressor in the context of T-ALL, and phenformin may have potential for the prevention of some cancers.

Dates et versions

hal-02348792 , version 1 (05-11-2019)

Identifiants

Citer

Diana Vara-Ciruelos, Madhumita Dandapani, Fiona Russell, Katarzyna Grzes, Abdelmadjid Atrih, et al.. Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation. Cell Reports, 2019, 27 (3), pp.690-698.e4. ⟨10.1016/j.celrep.2019.03.067⟩. ⟨hal-02348792⟩

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