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The differential activation of metabolic pathways in leukemic cells depending on their genotype and micro-environmental stress
- Source :
- Metabolomics, Metabolomics, Springer Verlag, 2020, 16 (1), ⟨10.1007/s11306-020-1633-z⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- Acute myeloid leukemia (AML) is characterized by a set of malignant proliferations leading to an accumulation of blasts in the bone marrow and blood. The prognosis is pejorative due to the molecular complexity and pathways implicated in leukemogenesis. Our research was focused on comparing the metabolic profiles of leukemic cells in basal culture and deprivation conditions to investigate their behaviors under metabolic stress. We performed untargeted metabolomics using 1H HRMAS-NMR. Five human leukemic cell lines—KG1, K562, HEL, HL60 and OCIAML3—were studied in the basal and nutrient deprivation states. A multivariate analysis of the metabolic profile was performed to find over- or under- expressed metabolites in the different cell lines, depending on the experimental conditions. In the basal state, each leukemic cell line exhibited a specific metabolic signature related to the diversity of AML subtypes represented and their phenotypes. When cultured in a serum-free medium, they showed quick metabolic adaptation and continued to proliferate and survive despite the lack of nutrients. Low apoptosis was observed. Increased phosphocholine and glutathione was a common feature of all the observed cell lines, with the maximum increase in these metabolites at 24 h of culture, suggesting the involvement of lipid metabolism and oxidative stress regulators in the survival mechanism developed by the leukemic cells. Our study provides new insights into the metabolic mechanisms in leukemogenesis and suggests a hierarchy of metabolic pathways activated within leukemic cells, some dependent on their genotypes and others conserved among the subtypes but commonly induced under micro-environmental stress.
- Subjects :
- Genotype
HL60
Endocrinology, Diabetes and Metabolism
[SDV]Life Sciences [q-bio]
Clinical Biochemistry
Cell
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
01 natural sciences
Biochemistry
Culture Media, Serum-Free
03 medical and health sciences
chemistry.chemical_compound
Metabolomics
Stress, Physiological
Cell Line, Tumor
medicine
Humans
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Leukemia
010401 analytical chemistry
Myeloid leukemia
0104 chemical sciences
Cell biology
Metabolic pathway
medicine.anatomical_structure
chemistry
Cell culture
Metabolome
Bone marrow
Metabolic Networks and Pathways
K562 cells
Subjects
Details
- Language :
- English
- ISSN :
- 15733882 and 15733890
- Database :
- OpenAIRE
- Journal :
- Metabolomics, Metabolomics, Springer Verlag, 2020, 16 (1), ⟨10.1007/s11306-020-1633-z⟩
- Accession number :
- edsair.doi.dedup.....dd701c706ced0bbb1cabd880dddae417
- Full Text :
- https://doi.org/10.1007/s11306-020-1633-z⟩