MassIVE MSV000100848

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Mouse-Plasma-Untargeted-LCHRMS-Metabolomic profile

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Description

FMS-like tyrosine kinase 3 (FLT3) mutations in acute myeloid leukemia (AML) are associated with adverseprognosis. FLT3 inhibitors (FLT3i) improve therapeutic response, however diverse resistance mechanisms such as adaptations in lipid metabolism have been identified. We hypothesized that a lipid-rich ketogenic diet (KD) might alter both host and tumoral lipid metabolism, enhancing responses to FLT3i. In FLT3-mutated AML mouse models, three weeks of lard- or plant-based KD improved efficacy of FLT3i by two-fold reduction of engraftment and tumor burden. KD increased ketone bodies and lipid accumulation inplasma, liver and AML cells, and also induced a PUFA:MUFA imbalance. KD impacted pentoses, hexoses and amino acid metabolism, enhancing sugar phosphates and vitamins in host. Mechanistically, KD rewired anabolism towards fatty acid oxidation and glycine-utilizing pathways, modulated the expression of FLT3 signaling pathways and lipid biosynthesis, and promoted tumor cell differentiation. In conclusion, this study shows that KD reduces FLT3i-resistance, offering a promising therapeutic solution. [doi:10.25345/C5319SG6W] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Plasma, Metabolimics, LC-HRMS, Acute myeloid leukemia, FLT3-ITD mutations, therapy resistance, metabolism, ketogenic diet ; DatasetType:Metabolomics

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Principal Investigators:
(in alphabetical order) 		CASTELLI Florence, CEA, France
Submitting User: fcastelli
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Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.