Supplementary Figures S1-S22 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in <i>FLT3</i>-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel 
Published: July 2023

<p>Supplemental figures S1-S22: Supplementary Figure S1 shows lipid metabolism dependency in FLT3-mutant AML, Supplementary Figure S2 shows anti-leukemic activity of GILT across a panel of AML PDX, Supplementary Figure S3 shows mechanisms of post-translational regulation of C/EBPα expression, Supplementary Figure S4 shows inhibition of C/EBPα phosphorylation and protein expression by FLT3i, Supplementary Figure S5 shows the implication of Ser-21 phosphorylation in post-translational regulation of C/EBPα expression, Supplementary Figure S6 shows that FLT3-ITD regulates the expression of C/EBPα and of proteins related to lipid biosynthesis in AML cell lines, Supplementary Figure S7 shows that FLT3-ITD regulates the expression of genes related to lipid biosynthesis in AML cell lines, Supplementary Figure S8 shows that C/EBPα directly regulates the transcription of lipid biosynthesis genes in AML, Supplementary Figure S9 shows the correlation between CEBPA mRNA expression and FLT3-ITD mutations, Supplementary Figure S10 shows scRNA-seq analysis from PDXTUH84, Supplementary Figure S11 shows scRNA-seq analysis from PDXTUH110, Supplementary Figure S12 shows the evolution of CEBPA_UP and FLT3-ITD_UP signatures in patients with AML treated with GILT, Supplementary Figure S13 shows that C/EBPα regulates rate-limiting lipid biosynthetic enzymes downstream of FLT3-ITD, Supplementary Figure S14 shows that C/EBPα controls lipid amount in FLT3-ITD cell lines, Supplementary Figure S15 shows that FLT3 inhibitors induce a lipid switch increasing neutral lipids dependent on C/EBPα, Supplementary Figure S16 shows that FLT3 inhibitor inhibits fatty acid synthesis fueled by glucose and glutamine, Supplementary Figure S17 shows that FLT3 inhibition decreases monounsaturated fatty acid dependent on C/EBPα, Supplementary Figure S18 shows that FLT3 inhibition increases PUFA/MUFA ratio dependent on C/EBPα, Supplementary Figure S19 shows that ferroptotic cell death induced by FLT3i is mediated by inhibition of SCD-dependent mono-unsaturated FA synthesis, Supplementary Figure S20 shows that FLT3 inhibitors unmask a vulnerability of FLT3-mutant leukemic cells to ferroptosis, Supplementary Figure S21 shows that lipid redox stress induction by GPX4 inhibition primed FLT3i activity in FLT3-ITD AML cells and Supplementary Figure S22 shows combined treatment with GILT and APR-246 in preclinical AML models in vivo.</p>