Su, Chang
(2021)
Proteomic study of the CD40 stimulation-induced pro-survival effect on chronic lymphocytic leukaemia cells.
PhD thesis, University of Liverpool.
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Abstract
The interactions between chronic lymphocytic leukaemia (CLL) cells and the CLL microenvironment play an important role in the disease progression and development of resistance to therapies. CD40 stimulation of CLL cells by T cells represents a major interaction in vivo, contributing to the survival and proliferation of CLL cells. However, the molecular mechanisms mediating these effects of CD40 stimulation are not fully understood. Through the proteomics approach, this project aimed to identify molecules/pathways associated with the pro-survival effect of CD40 stimulation by studying the global changes in protein expression in CD40 stimulated CLL cells. Herein, it was independently confirmed that CD40 stimulation protected CLL cells from spontaneous and drug-induced cell death. Mass spectrometry-based proteomic study identified 552 proteins that were differentially expressed in the CD40 stimulated CLL cells in comparison with their unstimulated counterparts. Bioinformatics analysis showed that these differentially expressed proteins were involved in a variety of biological processes. The functional enrichment analysis of the significantly up-regulated proteins identified the ‘cell-cell adhesions’ at the top of a list of the most enriched functional clusters. This cluster included 38 differentially expressed proteins, 17 of them with over 2-fold changes in protein expression. Among the proteins with over 2-fold changes in expression was the ATP-dependent RNA helicase DDX3X. The preliminary functional study suggested that DDX3X potentially plays a role in the CD40 stimulation-mediated survival of CLL cells. Taken together, these data indicated that CD40 stimulation produced the pro-survival effect by enhancing the cell adhesion properties of CLL cells. Therefore, the findings from this study have provided a reasonable foundation for future studies to investigate the molecular mechanisms responsible for the CD40 stimulation-mediated survival of CLL cells, which could help identify potential targets for therapeutic intervention to overcome the CD40 stimulation-induced drug resistance in CLL.
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Mar 2021 15:39 |
| Last Modified: | 18 Jan 2023 22:57 |
| DOI: | 10.17638/03116494 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3116494 |
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