The role and regulation of AKT in CD40-mediated survival and proliferation of CLL cells

Chapman, EA ORCID: 0000-0002-4398-1705 (2016) The role and regulation of AKT in CD40-mediated survival and proliferation of CLL cells. PhD thesis, University of Liverpool.

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Abstract

Chronic lymphocytic leukaemia (CLL) is a proliferative disease in which malignant B lymphocytes gradually accumulate in the peripheral blood, lymph nodes and bone marrow. It is the most common leukaemia in adults and currently incurable. Novel therapeutic strategies are thus required. The serine/threonine kinase AKT has been shown to contribute to the survival and expansion of CLL cells. However, the exact role of AKT in CD40 stimulation-induced survival and proliferation of CLL cells is not well understood. The aim of this study was to investigate how AKT mediates CLL-cell survival and proliferation, in particular under the conditions that mimic the protective tissue microenvironment in vivo. I therefore used a co-culture system in which primary CLL cells were cultured with transfected mouse fibroblasts expressing human CD154 to model the lymph node environment where CLL cells interact with T cells through the CD40-CD154 signalling pathway, resulting in their enhanced survival and proliferation. I showed that AKT was activated in CD40-stimulated CLL cells. AKT mediated a protective effect of CD40 stimulation against cytotoxic drug (bendamustine)-induced cell death, as inhibiting AKT activity by a selective, ... (continues)

Item Type:	Thesis (PhD)
Divisions:	Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	10 Aug 2016 08:24
Last Modified:	30 Sep 2024 02:15
DOI:	10.17638/03001683
Supervisors:	Zhuang, J ORCID: 0000-0003-3245-0789 Pettitt, A ORCID: 0000-0002-0907-8950 Davies, B
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3001683