Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells.
acute myeloid leukaemia
biochemistry
cancer biology
chemical biology
human
metabolism
microenvironment
mouse
nuclear magnetic resonance
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
received:
26
11
2021
accepted:
01
09
2022
pubmed:
3
9
2022
medline:
20
9
2022
entrez:
2
9
2022
Statut:
epublish
Résumé
Acute 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.
Identifiants
pubmed: 36052997
doi: 10.7554/eLife.75908
pii: 75908
pmc: PMC9477493
doi:
pii:
Substances chimiques
Acetates
0
Lipids
0
Pyruvates
0
Reactive Oxygen Species
0
Banques de données
GEO
['GSE163478', 'GSE128423']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/P019609/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 208400/Z/17/Z
Pays : United Kingdom
Informations de copyright
© 2022, Vilaplana-Lopera et al.
Déclaration de conflit d'intérêts
NV, VC, RA, GP, AR, MJ, EG, YA, AC, AE, FS, MR, SP, JC, JS, MR, LA, UG, PG No competing interests declared
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