Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress
In vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stres...
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doaj-69f6f55d1b8e44f4821c4839eca809862021-09-26T00:15:36ZengMDPI AGHemato2673-63572021-09-0123960762710.3390/hemato2030039Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum StressElise Aasebø0Annette K. Brenner1Maria Hernandez-Valladares2Even Birkeland3Håkon Reikvam4Frode Selheim5Frode S. Berven6Øystein Bruserud7Department of Clinical Science, University of Bergen, 5020 Bergen, NorwayDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayThe Proteomics Facility of the University of Bergen (PROBE), University of Bergen, 5020 Bergen, NorwayThe Proteomics Facility of the University of Bergen (PROBE), University of Bergen, 5020 Bergen, NorwayDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayThe Proteomics Facility of the University of Bergen (PROBE), University of Bergen, 5020 Bergen, NorwayThe Proteomics Facility of the University of Bergen (PROBE), University of Bergen, 5020 Bergen, NorwayDepartment of Clinical Science, University of Bergen, 5020 Bergen, NorwayIn vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stress-induced apoptosis varies between patients, and a high degree of apoptosis is associated with high pre-culture BCL2 levels together with low levels of BAX and Heat Shock Proteins 30 and 90. We compared the global proteomic profiles during ongoing in vitro apoptosis for patients with high and low AML cell viability (i.e., less extensive versus extensive spontaneous apoptosis) after 48 h of culture. We identified 7902 proteins, but only 276 proteins differed significantly between patients with high (i.e., >25% viable cells; 192 upregulated and 84 downregulated peptides) and low viability after in vitro culture. Protein interaction network analysis based on these 276 protein identified three protein networks that included 18 proteins; most of these proteins were localized to the endoplasmic reticulum and several of them are involved in or are altered during the process of endoplasmic reticulum stress/unfolded protein stress response. To conclude, primary AML cells are heterogeneous with regard to degree of apoptosis in response to cellular stress, and this difference in regulation of apoptosis is associated with differences in the induction of and/or response to the unfolded protein stress response.https://www.mdpi.com/2673-6357/2/3/39acute myeloid leukemiaapoptosisendoplasmic reticulumproteomic profile |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elise Aasebø Annette K. Brenner Maria Hernandez-Valladares Even Birkeland Håkon Reikvam Frode Selheim Frode S. Berven Øystein Bruserud |
spellingShingle |
Elise Aasebø Annette K. Brenner Maria Hernandez-Valladares Even Birkeland Håkon Reikvam Frode Selheim Frode S. Berven Øystein Bruserud Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress Hemato acute myeloid leukemia apoptosis endoplasmic reticulum proteomic profile |
author_facet |
Elise Aasebø Annette K. Brenner Maria Hernandez-Valladares Even Birkeland Håkon Reikvam Frode Selheim Frode S. Berven Øystein Bruserud |
author_sort |
Elise Aasebø |
title |
Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress |
title_short |
Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress |
title_full |
Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress |
title_fullStr |
Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress |
title_full_unstemmed |
Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress |
title_sort |
proteomic characterization of spontaneous stress-induced in vitro apoptosis of human acute myeloid leukemia cells; focus on patient heterogeneity and endoplasmic reticulum stress |
publisher |
MDPI AG |
series |
Hemato |
issn |
2673-6357 |
publishDate |
2021-09-01 |
description |
In vitro culture is widely used for characterization of primary human acute myeloid leukemia (AML) cells, but even when using optimized handling and culture conditions the AML cells show spontaneous in vitro apoptosis with a gradual decrease in cell viability during culture. The extent of this stress-induced apoptosis varies between patients, and a high degree of apoptosis is associated with high pre-culture BCL2 levels together with low levels of BAX and Heat Shock Proteins 30 and 90. We compared the global proteomic profiles during ongoing in vitro apoptosis for patients with high and low AML cell viability (i.e., less extensive versus extensive spontaneous apoptosis) after 48 h of culture. We identified 7902 proteins, but only 276 proteins differed significantly between patients with high (i.e., >25% viable cells; 192 upregulated and 84 downregulated peptides) and low viability after in vitro culture. Protein interaction network analysis based on these 276 protein identified three protein networks that included 18 proteins; most of these proteins were localized to the endoplasmic reticulum and several of them are involved in or are altered during the process of endoplasmic reticulum stress/unfolded protein stress response. To conclude, primary AML cells are heterogeneous with regard to degree of apoptosis in response to cellular stress, and this difference in regulation of apoptosis is associated with differences in the induction of and/or response to the unfolded protein stress response. |
topic |
acute myeloid leukemia apoptosis endoplasmic reticulum proteomic profile |
url |
https://www.mdpi.com/2673-6357/2/3/39 |
work_keys_str_mv |
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