Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on Stearoyl CoA desaturase

Savino, A. M. et al. (2020) Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on Stearoyl CoA desaturase. Nature Cancer, 1(10), pp. 998-1009. (doi: 10.1038/s43018-020-00115-2) (PMID:33479702) (PMCID:PMC7116605)

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Metabolic reprogramming is a key hallmark of cancer, but less is known about metabolic plasticity of the same tumor at different sites. Here, we investigated the metabolic adaptation of leukemia in two different microenvironments, the bone marrow and the central nervous system (CNS). We identified a metabolic signature of fatty acid synthesis in CNS leukemia, highlighting stearoyl-CoA desaturase (SCD) as a key player. In vivo SCD overexpression increases CNS disease, whereas genetic or pharmacological inhibition of SCD decreases CNS load. Overall, we demonstrated that leukemic cells dynamically rewire metabolic pathways to suit local conditions and that targeting these adaptations can be exploited therapeutically.

Item Type:Articles
Additional Information:This work was supported by the Chief Scientist Office (O.O. and C.H., grant ETM/374), Fondazione Italiana per la Ricerca sul Cancro *FIRC (A.M.S.), the William and Elizabeth Davies Foundation (A.C., Clinical Research Fellowship), the Laura and Ike Perlmutter Fund (E.G. and I.A.), the German Israel Foundation (S.I. and C.E.), the Norman and Sadie Lee Foundation (S.I.), the Israel Science Foundation 1775/12 (E.G. and I.M.), European Union ERA NET TRASCALL program (S.I.), Israel Cancer Research Foundation City of Hope collaborative program (S.I.) and Cancer Research UK (J.J.K. and G.M.). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement META-CAN No 766214 (S.I.F., J.F-G., I.M. and E.G.).
Glasgow Author(s) Enlighten ID:Kamphorst, Dr Jurre and Olivares, Miss Orianne and Cousins, Dr Antony and Mor, Dr Inbal and Markert, Dr Elke and Halsey, Professor Chris and Gottlieb, Professor Eyal and Herzyk, Dr Pawel and Tumanov, Dr Sergey and Mackay, Dr Gillian
Authors: Savino, A. M., Fernandes, S. I., Olivares, O., Zemlyansky, A., Cousins, A., Markert, E. K., Barel, S., Geron, I., Frishman, L., Birger, Y., Eckert, C., Tumanov, S., MacKay, G., Kamphorst, J. J., Herzyk, P., Fernández-García, J., Abramovich, I., Mor, I., Bardini, M., Barin, E., Janaki-Raman, S., Cross, J. R., Kharas, M. G., Gottlieb, E., Izraeli, S., and Halsey, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Nature Cancer
Publisher:Nature Research
ISSN (Online):2662-1347
Published Online:28 September 2020
Copyright Holders:Copyright © 2020 Springer Nature Limited
First Published:First published in Nature Cancer 1(10): 998-1009
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190794Identifying Novel Targets for eradication of acute lymphoblastic leukaemia in the central nervous systemChristina HalseyChief Scientist Office (CSO)ETM/374III - Immunology