Molecular mechanisms conferring resistance/sensitivity to glucocorticoid-induced apoptosis

Berrou, Ilhem; Krstic-Demonacos, Marija; Demonacos, Constantinos

Abstract

Resistance to glucocorticoid induced apoptosis in acute lymphoblastic leukaemia (ALL) has been attributed to several different processes and pathways including predominance of certain GR isoforms with reduced transcriptional activity, either due to altered binding capacity of the receptor to other transcription factors or co-regulators, disparate expression and consequent dissimilar balance between pro- versus anti-apoptotic members of the Bcl-2 family, GR mitochondrial localisation, autophagy, and post-translational modifications which affect GR transcription target selectivity and protein stability differential GR phosphorylation affects components of cellular energy production pathways in distinct ways in resistant versus sensitive cells altering energy production and possibly ROS generation in unique ways in the two cell lines, suggesting that combination of kinase inhibitors, and glycolytic modulators together with dexamethasone could be a possible mean by which resistance to glucocorticoid induced apoptosis could be circumvented in ALL.

• Deposit Date: Mar 6, 2019
• Publicly Available Date: Mar 6, 2019
• Peer Reviewed: Peer Reviewed
• Book Title: Glucocorticoids - New Recognition of Our Familiar Friend
• DOI: https://doi.org/10.5772/51467
• Public URL: https://uwe-repository.worktribe.com/output/951578
• Publisher URL: http://dx.doi.org/10.5772/51467
• Contract Date: Mar 6, 2019