**4. Conclusions**

The combination of proteomics, lipidomics, and isotopic profiling experiments allowed us to uncover a profound reprogramming of lipid metabolism in IDH1 mutant AML cells through a simultaneous increase of both FA oxidation and de novo lipogenesis. This reprogramming is—at least partly- dependent on 2-HG production, which controls FAS expression. Integration of all of these omics data in an AML metabolic network could allow fluxes calculations to gain even more insight into the metabolic regulation of IDH WT and R132H cells.

#### **Supplementary Materials:** The following are available online at http://www.mdpi.com/1422-0067/19/11/3325/ s1.

**Author Contributions:** Conceptualization, J.-E.S., J.-C.P. and J.B.-M.; methodology, J.B.-M., F.R. and L.S.; software, P.M.; validation, F.R., A.B. and L.S.; formal analysis, M.S. and F.R.; investigation, F.R, A.B., F.V., L.T., S.Z., E.S., L.K.L. and L.S.; resources, L.S., P.M. and E.S.; data curation, P.M.; writing—original draft preparation, L.S. and J.B.-M.; writing—review and editing, L.S, P.M., J.-C.P., J.-E.S. and J.B.-M.; visualization, L.S., M.S. and J.B.-M.; supervision, J.-E.S. and J.B.-M. project administration, J.B.-M. and L.S.; funding acquisition, J.-E.S. and J.-C.P.

**Funding:** This work was supported by grants from the Région Midi-Pyrénées (CRLE; J.-E.S.), Plan Cancer 2014-BioSys (FLEXAML; J.-E.S.) and the Institut national de la santé et de la recherche médicale (Inserm). MetaToul is part of the national infrastructure MetaboHUB (The French National infrastructure for metabolomics and fluxomics, www.metabohub.fr) and is supported by MetaboHUB-ANR-11-INBS-0010, by the Région Occitanie, the European Regional Development Fund, the SICOVAL, the Infrastructures en Biologie Sante et Agronomie (IBiSa, France), the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Recherche Agronomique (INRA) and Inserm.

**Acknowledgments:** MetaToul (Metabolomics & Fluxomics Facitilies, Toulouse, France, www.metatoul.fr) is gratefully acknowledged for carrying out metabolome et lipdiomic analysis.

**Conflicts of Interest:** The authors declare no conflict of interest.
