Proteomic Characterization of Spontaneous Stress-Induced In Vitro Apoptosis of Human Acute Myeloid Leukemia Cells; Focus on Patient Heterogeneity and Endoplasmic Reticulum Stress
Open Access
- 17 September 2021
- Vol. 2 (3), 607-627
- https://doi.org/10.3390/hemato2030039
Abstract
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.Keywords
Funding Information
- Kreftforeningen (100933, 182609)
- Norges Forskningsråd (295910)
This publication has 78 references indexed in Scilit:
- The pterocarpanquinone LQB 118 induces apoptosis in tumor cells through the intrinsic pathway and the endoplasmic reticulum stress pathwayAnti-Cancer Drugs, 2013
- Thymidine Analogues for Tracking DNA SynthesisMolecules, 2011
- Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012Cell Death & Differentiation, 2011
- Enhanced Lysosomal Activity Is Involved in Bax Inhibitor-1-induced Regulation of the Endoplasmic Reticulum (ER) Stress Response and Cell Death against ER StressOnline Journal of Public Health Informatics, 2011
- Melanoma Differentiation Associated Gene-7/Interleukin-24 Potently Induces Apoptosis in Human Myeloid Leukemia Cells through a Process Regulated by Endoplasmic Reticulum StressMolecular Pharmacology, 2010
- The proteasome inhibitors bortezomib and PR‐171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cellsBritish Journal of Haematology, 2007
- Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cellsBiochemical and Biophysical Research Communications, 2007
- Endoplasmic reticulum stress: cell life and death decisionsJCI Insight, 2005
- Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction NetworksGenome Research, 2003
- In Vitro Culture of Acute Myelogenous Leukemia Blasts: A Comparison of Four Different Culture MediaJournal of Hematotherapy, 1999