Keadsanti, S
(2018)
The chemokine regulation of Bruton's tyrosine kinase in acute myeloid leukaemia.
PhD thesis, University of Liverpool.
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Abstract
Acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL) are common in the elderly. Bruton's tyrosine kinase (BTK) is an important protein that plays a vital role in several signalling pathways including the B cell receptor (BCR) and SDF-1α/CXCR4 chemokine signalling pathways. Although BTK is a cytoplasmic tyrosine kinase the protein can also found in the nucleus. Thus, the nuclear-cytoplasmic shuttling mechanism of BTK and BTK-binding protein are proposed in other studies, but BTK's actual role in the nucleus is still unclear. Therefore, the first aspect of this study examined BTK and p-BTK in the cytoplasm and nucleus of AML and CLL cells. AML and CLL cellular fractionation showed that BTK and p-BTK were detected in both cytoplasm and nuclear fractions. Thus, BTK may perform important functional roles in their nuclei. The second aspect of this study focused on the SDF-1α/CXCR4 signalling pathway which is important for AML survival and may control cellular responses through BTK. We identified which Gα12 subclasses can couple with CXCR4 receptor to convey the signalling of BTK, in addition to Gαi-linked signalling seen in AML. Results showed CXCR4 was expressed in AML and CLL, and that BTK ... (continues)
| Item Type: | Thesis (PhD) |
|---|---|
| Divisions: | Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 22 Nov 2018 10:59 |
| Last Modified: | 30 Sep 2024 02:15 |
| DOI: | 10.17638/03026287 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3026287 |
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