Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells
Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
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| Enthalten in: |
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi - 44(2023), 5 vom: 14. Mai, Seite 366-372 |
| Sprache: |
Chinesisch |
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| Beteiligte Personen: |
Xie, W Q [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.08.2023 Date Revised 23.08.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.3760/cma.j.issn.0253-2727.2023.05.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360498418 |
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| 245 | 1 | 0 | |a Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 09.08.2023 | ||
| 500 | |a Date Revised 23.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered | ||
| 650 | 4 | |a English Abstract | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AML1-ETO fusion gene | |
| 650 | 4 | |a Fatty acid metabolism | |
| 650 | 4 | |a Leukemia, myeloid, acute | |
| 650 | 4 | |a Tet-on system | |
| 650 | 4 | |a U937 cells | |
| 650 | 7 | |a RUNX1 Translocation Partner 1 Protein |2 NLM | |
| 650 | 7 | |a acylcarnitine |2 NLM | |
| 650 | 7 | |a Core Binding Factor Alpha 2 Subunit |2 NLM | |
| 650 | 7 | |a Oncogene Proteins, Fusion |2 NLM | |
| 650 | 7 | |a AML1-ETO fusion protein, human |2 NLM | |
| 700 | 1 | |a Yang, X |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, R X |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Z |e verfasserin |4 aut | |
| 700 | 1 | |a Xing, H Y |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, K J |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Q |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, S W |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, J X |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi |d 1993 |g 44(2023), 5 vom: 14. Mai, Seite 366-372 |w (DE-627)NLM081873417 |x 0253-2727 |7 nnns |
| 773 | 1 | 8 | |g volume:44 |g year:2023 |g number:5 |g day:14 |g month:05 |g pages:366-372 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2023.05.003 |3 Volltext |
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