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dc.contributor.authorVilaplana-Lopera, Nuria
dc.contributor.authorCuminetti, Vincent
dc.contributor.authorAlmaghrabi, Ruba
dc.contributor.authorPapatzikas, Grigorios
dc.contributor.authorRout, Ashok Kumar
dc.contributor.authorJeeves, Mark
dc.contributor.authorGonzález, Elena
dc.contributor.authorAlyahyawi, Yara
dc.contributor.authorCunningham, Alan
dc.contributor.authorErdem, Ayşegül
dc.contributor.authorSchnütgen, Frank
dc.contributor.authorRaghavan, Manoj
dc.contributor.authorPotluri, Sandeep
dc.contributor.authorCazier, Jean-Baptiste
dc.contributor.authorSchuringa, Jan Jacob
dc.contributor.authorReed, Michelle AC
dc.contributor.authorArranz, Lorena
dc.contributor.authorGünther, Ulrich L
dc.contributor.authorGarcia, Paloma
dc.description.abstractAcute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, whether AML cells could establish beneficial metabolic interactions with stromal cells is underexplored. By using a combination of human AML cell lines and AML patient samples together with mouse stromal cells and a MLL-AF9 mouse model, here we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption to feed the tricarboxylic acid cycle (TCA) and lipid biosynthesis. By performing transcriptome analysis and tracer-based metabolic NMR analysis, we observe that stromal cells present a higher rate of glycolysis when co-cultured with AML cells. We also find that acetate in stromal cells is derived from pyruvate via chemical conversion under the influence of reactive oxygen species (ROS) following ROS transfer from AML to stromal cells via gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells and propose two different molecular targets, ACSS2 and gap junctions, that could potentially be exploited for adjuvant therapy.en_US
dc.identifier.citationVilaplana-Lopera, Cuminetti, Almaghrabi, Papatzikas, Rout, Jeeves, González, Alyahyawi, Cunningham, Erdem, Schnütgen, Raghavan, Potluri, Cazier, Schuringa, Reed, Arranz, Günther, Garcia. Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells. eLIFE. 2022;11:1-29en_US
dc.identifier.cristinIDFRIDAID 2052890
dc.publishereLife Sciences Publicationsen_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/675790/EU/Deciphering the Metabolism of Haematological Cancers/HaemMetabolome/en_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleCrosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cellsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)