Rani Pallavi, Elena Gatti, Tiphanie Durfort, Massimo Stendardo, Roberto Ravasio, Tommaso Leonardi, Paolo Falvo, Bruno Achutti Duso, Simona Punzi, Aobuli Xieraili, Andrea Polazzi, Doriana Verrelli, Deborah Trastulli, Simona Ronzoni, Simone Frascolla, Giulia Perticari, Mohamed Elgendy, Mario Varasi, Emanuela Colombo, Marco Giorgio, Luisa Lanfrancone, Saverio Minucci, Luca Mazzarella, Pier Giuseppe Pelicci
Caloric Restriction (CR) has established anti-cancer effects, but its clinical relevance and molecular mechanism remain largely undefined. Here, we investigate CR's impact on several mouse models of Acute Myeloid Leukemias, including Acute Promyelocytic Leukemia, a subtype strongly affected by obesity. After an initial marked anti-tumor effect, lethal disease invariably re-emerges. Initially, CR leads to cell-cycle restriction, apoptosis, and inhibition of TOR and insulin/IGF1 signaling. The relapse, instead, is associated with the non-genetic selection of Leukemia Initiating Cells and the downregulation of double-stranded RNA (dsRNA) sensing and Interferon (IFN) signaling genes...
January 27, 2024: Nature Communications