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This thesis applies systems biology approaches to obtain a better understanding of complex cellular systems in Chronic Lymphocytic Leukaemia (CLL).CLL is a cancer of the blood which affects B cells. CLL cells accumulate quickly in the body but die rapidly by apoptosis when cultured in the lab, suggesting that CLL cell survival can be modulated by tumour cell interactions with the microenvironment in vivo. The first part of the thesis describes in vitro assays which demonstrated that CLL cell contact with endothelial cells in a co-culture system promotes CLL cell survival. The precise mechanisms involved remain unknown, however, they are thought to include both secreted factors and receptor:ligand interactions between CLL cells and the microenvironment. The second part of the thesis is based on gene expression profiling and investigates the transcriptional effects induced in CLL cells by co-culture. We identified genes that were statistically significantly up regulated >1.5 fold compared with liquid culture (q |
