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

Angela Maria Savino; Sara Isabel Fernandes; Orianne Olivares; Anna Zemlyansky; Antony Cousins; Elke K. Markert; Shani Barel; Ifat Geron; Liron Frishman; Yehudit Birger; Cornelia Eckert; Sergey Tumanov; Gillian MacKay; Jurre J. Kamphorst; Pawel Herzyk; Jonatan Fernández-García; Ifat Abramovich; Inbal Mor; Michela Bardini; Ersilia Barin; Sudha Janaki-Raman; Justin R. Cross; Michael G. Kharas; Eyal Gottlieb; Shai Izraeli; Christina Halsey

doi:10.1038/s43018-020-00115-2

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

Angela Maria Savino, Sara Isabel Fernandes, Orianne Olivares, Anna Zemlyansky, Antony Cousins, Elke K. Markert, Shani Barel, Ifat Geron, Liron Frishman, Yehudit Birger, Cornelia Eckert, Sergey Tumanov, Gillian MacKay, Jurre J. Kamphorst, Pawel Herzyk, Jonatan Fernández-García, Ifat Abramovich, Inbal Mor, Michela Bardini, Ersilia BarinSudha Janaki-Raman, Justin R. Cross, Michael G. Kharas, Eyal Gottlieb, Shai Izraeli, Christina Halsey

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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.

Original language	English
Pages (from-to)	998-1009
Number of pages	12
Journal	Nature Cancer
Volume	1
Issue number	10
DOIs	https://doi.org/10.1038/s43018-020-00115-2
State	Published - 1 Oct 2020
Externally published	Yes

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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., ... Halsey, C. (2020). Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase. Nature Cancer, 1(10), 998-1009. https://doi.org/10.1038/s43018-020-00115-2

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title = "Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase",

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.",

author = "Savino, {Angela Maria} and Fernandes, {Sara Isabel} and Orianne Olivares and Anna Zemlyansky and Antony Cousins and Markert, {Elke K.} and Shani Barel and Ifat Geron and Liron Frishman and Yehudit Birger and Cornelia Eckert and Sergey Tumanov and Gillian MacKay and Kamphorst, {Jurre J.} and Pawel Herzyk and Jonatan Fern{\'a}ndez-Garc{\'i}a and Ifat Abramovich and Inbal Mor and Michela Bardini and Ersilia Barin and Sudha Janaki-Raman and Cross, {Justin R.} and Kharas, {Michael G.} and Eyal Gottlieb and Shai Izraeli and Christina Halsey",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

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doi = "10.1038/s43018-020-00115-2",

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Savino, AM, Fernandes, SI, Olivares, O, Zemlyansky, A, Cousins, A, Markert, EK, Barel, S, Geron, I, Frishman, L, Birger, Y, Eckert, C, Tumanov, S, MacKay, G, Kamphorst, JJ, Herzyk, P, Fernández-García, J, Abramovich, I, Mor, I, Bardini, M, Barin, E, Janaki-Raman, S, Cross, JR, Kharas, MG, Gottlieb, E, Izraeli, S & Halsey, C 2020, 'Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase', Nature Cancer, vol. 1, no. 10, pp. 998-1009. https://doi.org/10.1038/s43018-020-00115-2

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AU - Cousins, Antony

AU - Markert, Elke K.

AU - Barel, Shani

AU - Geron, Ifat

AU - Frishman, Liron

AU - Birger, Yehudit

AU - Eckert, Cornelia

AU - Tumanov, Sergey

AU - MacKay, Gillian

AU - Kamphorst, Jurre J.

AU - Herzyk, Pawel

AU - Fernández-García, Jonatan

AU - Abramovich, Ifat

AU - Mor, Inbal

AU - Bardini, Michela

AU - Barin, Ersilia

AU - Janaki-Raman, Sudha

AU - Cross, Justin R.

AU - Kharas, Michael G.

AU - Gottlieb, Eyal

AU - Izraeli, Shai

AU - Halsey, Christina

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

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