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.

Savino, A., Fernandes, S., Olivares, O., Zemlyansky, A., Cousins, A., Markert, E., et al. (2020). Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment is dependent on Stearoyl CoA desaturase. NATURE CANCER, 1(10), 998-1009 [10.1038/s43018-020-00115-2].

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

Savino, Angela Maria
Co-primo
;
Bardini, Michela;
2020

Abstract

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
SCD1; acute lymphoblastic leukemia; central nervous system; fatty acid synthesis; metabolic reprogramming; Central Nervous System; Humans; Lipogenesis; Tumor Microenvironment; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Stearoyl-CoA Desaturase
English
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1009
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Savino, A., Fernandes, S., Olivares, O., Zemlyansky, A., Cousins, A., Markert, E., et al. (2020). Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment is dependent on Stearoyl CoA desaturase. NATURE CANCER, 1(10), 998-1009 [10.1038/s43018-020-00115-2].
Savino, A; Fernandes, S; Olivares, O; Zemlyansky, A; Cousins, A; Markert, E; Barel, S; Geron, I; Frishman, L; Birger, Y; Eckert, C; Tumanov, S; Mackay, G; Kamphorst, J; Herzyk, P; Fernández-García, J; Abramovich, I; Mor, I; Bardini, M; Barin, E; Janaki-Raman, S; Cross, J; Kharas, M; Gottlieb, E; Izraeli, S; Halsey, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/391311
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