3095 – OXPHOS-DRIVEN LEUKEMIC STEM CELLS ARE UNIQUELY SENSITIVE TO COLD EXPOSURE

• Published in: Experimental hematology 2022, Vol.111, p.S92-S92
• Main Authors: Griessinger, Emmanuel, Nebout, Marielle, Pereira-Martins, Diego, Bosc, Claudie, Saland, Estelle, Boet, Emilie, Sahal, Ambrine, Chiche, Johanna, Debayle, Delphine, Fleuriot, Lucille, DeMas, Véronique, Vergez, François, Récher, Christian, Huls, Gerwin, Sarry, Jean-Emmanuel, Schuringa, Jan Jacob, Peyron, Jean-François
• Format: Article
• Language: English
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2022.07.151

Metabolic heterogeneity within the same tumour entity influences treatment and promotes cancer progression. Identifying metabolic vulnerabilities is an appealing effort to develop novel therapeutic and diagnostic approaches. Here, we uncover that in Acute Myeloid Leukemia (AML) cells relying on mitochondrial oxidative phosphorylation (OxPhos) are sensitive to cold exposure, whereas AML cells relying on glycolysis are cold resistant. Forcing glycolytic cells towards an OxPhos metabolism sensitized them to cold exposure. This difference in sensitivity is independent of the level of cholesterol. Fatty acid oxidative metabolism shapes the plasma membrane composition and underlies differences in cold sensitivity. We assayed the Cold killing challenge at 4°C (CKC4) in 55 primary AML samples and confirmed by quantitative proteome that Cold-sensitive AML patient samples were significantly enriched for fatty acid beta oxidation and OxPhos. Eventually we report that HSC-like AMLs cells are more sensitive to CKC4 as compared to MEP-like, CMP-like, GMP-like, LMPP-like cells or compared to normal HSCs. This novel property of cancer cells and LSCs and the CKC4 represent a promising opportunity in the field of oncometabolism for patient diagnostic and LSCs targeting.