Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells

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 int...

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Veröffentlicht in:eLife Jg. 11
Hauptverfasser: Vilaplana-Lopera, Nuria, Cuminetti, Vincent, Almaghrabi, Ruba, Papatzikas, Grigorios, Rout, Ashok Kumar, Jeeves, Mark, González, Elena, Alyahyawi, Yara, Cunningham, Alan, Erdem, Ayşegül, Schnütgen, Frank, Raghavan, Manoj, Potluri, Sandeep, Cazier, Jean-Baptiste, Schuringa, Jan Jacob, Reed, Michelle AC, Arranz, Lorena, Günther, Ulrich L, Garcia, Paloma
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England eLife Sciences Publications Ltd 02.09.2022
eLife Sciences Publications, Ltd
Schlagworte:
Acetates
Acetic acid
acute myeloid leukaemia
Acute myeloid leukemia
Animals
Biochemistry and Chemical Biology
Bone marrow
Cancer Biology
Cell interactions
Cell lines
Experiments
Gap junctions
Glucose
Glycolysis
human
Humans
Leukemia, Myeloid, Acute - metabolism
Lipids
Metabolism
Metabolites
Mice
microenvironment
Microenvironments
mouse
NMR
Nuclear magnetic resonance
Pyruvates
Pyruvic acid
Reactive oxygen species
Reactive Oxygen Species - metabolism
Signal Transduction
Standard deviation
Stromal cells
Stromal Cells - metabolism
Transcriptomes
Tricarboxylic acid cycle
Tumor Microenvironment
microenvironment
mouse
chemical biology
acute myeloid leukaemia
biochemistry
cancer biology
metabolism
human
nuclear magnetic resonance
ISSN:2050-084X, 2050-084X
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Zusammenfassung: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.
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These authors contributed equally to this work.
Co-senior author.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.75908