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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)998-1009
Number of pages12
JournalNature Cancer
Volume1
Issue number10
DOIs
StatePublished - 1 Oct 2020

Fingerprint

Dive into the research topics of 'Metabolic adaptation of acute lymphoblastic leukemia to the central nervous system microenvironment depends on stearoyl-CoA desaturase'. Together they form a unique fingerprint.

Cite this