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

Author

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

Subjects
Central Nervous System, Cancer Research, Central nervous system, acute lymphoblastic leukemia, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, hemic and lymphatic diseases, medicine, Tumor Microenvironment, metabolic reprogramming, Humans, Fatty acid synthesis, 030304 developmental biology, 0303 health sciences, Lipogenesis, Lipogenesi, Cancer, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, 3. Good health, Leukemia, Stearoyl-CoA Desaturase, Metabolic pathway, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, Cancer research, fatty acid synthesi, lipids (amino acids, peptides, and proteins), Bone marrow, SCD1, Human
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 (SCD1) as a key player. In vivo SCD1 overexpression increases CNS disease, whilst genetic or pharmacological inhibition of SCD1 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.

Published
2020
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