Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase Journal Article
| 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-Garcia, J.; Abramovich, I.; Mor, I.; Bardini, M.; Barin, E.; Janaki-Raman, S.; Cross, J. R.; Kharas, M. G.; Gottlieb, E.; Izraeli, S.; Halsey, C. |
| Article 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. Gottlieb and colleagues show that stearoyl-CoA desaturase promotes metabolic adaptation of acute lymphoblastic leukemia cells to the central nervous system microenvironment, revealing a potential site-specific metabolic vulnerability of this disease. |
| Keywords: | survival; childhood; stem-cells; inhibitors; heterogeneity; cns; discovery; involvement; cerebrospinal-fluid; infiltration |
| Journal Title: | Nature Cancer |
| Volume: | 1 |
| Issue: | 10 |
| ISSN: | 2662-1347 |
| Publisher: | Nature Research |
| Date Published: | 2020-10-01 |
| Start Page: | 998 |
| End Page: | 1009 |
| Language: | English |
| ACCESSION: | WOS:000614880800009 |
| DOI: | 10.1038/s43018-020-00115-2 |
| PROVIDER: | wos |
| PMCID: | PMC7116605 |
| PUBMED: | 33479702 |
| Notes: | Article -- Source: Wos |
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