GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue CELL METABOLISM Année : 2019

GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors

Annabelle Mouchotte
  • Fonction : Auteur
Jozef P. Bossowski
  • Fonction : Auteur
Manuel Grima-Reyes
  • Fonction : Auteur
Damien Ambrosetti
Eric De Kerviler
  • Fonction : Auteur
Bruno Taillan
  • Fonction : Auteur

Résumé

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism(phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism-using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors.

Domaines

Immunologie
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Dates et versions

hal-02359440 , version 1 (25-10-2021)

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Paternité - Pas d'utilisation commerciale

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Johanna Chiche, Julie Reverso-Meinietti, Annabelle Mouchotte, Camila Rubio-Patino, Rana Mhaidly, et al.. GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors. CELL METABOLISM, 2019, 29 (6), pp.1243+. ⟨10.1016/j.cmet.2019.02.002⟩. ⟨hal-02359440⟩
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