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ZAP-70 Phosphorylation and other prognostic factors in adult B-chronic lymphocytic leukaemia patients

Maramba, Aaron

ZAP-70 Phosphorylation and other prognostic factors in adult B-chronic lymphocytic leukaemia patients Thumbnail


Authors

Aaron Maramba



Abstract

Abstract
B chronic lymphocytic leukaemia (B-CLL) is a disease with an enormously heterogeneous prognosis. Due to lack of effective treatments and the heterogeneity in its course, B-CLL has remained largely incurable. In the last two decades a number of biological markers have been recognised as prognostic parameters to replace clinical staging, chief among them is ZAP-70 (a T-cell cytoplasmic tyrosine protein) albeit without a full understanding of the mechanism involved.

The aim of this thesis was to identify reliable prognostic factors that could be used in the management of B-CLL patients. Seventy-six B-CLL patients were studied over 30 months using a random stratified method of sampling, whereby adult B-CLL patients were recruited at different stages of the disease. Retrospective studies enabled some patients to be studied for up to 192 months. ZAP-70 expression was demonstrated in some B-CLL cells and was examined for possible phosphorylation following B-CLL cells stimulation, implying its involvement in cell signalling. Through the use of a novel method developed during the present study, B-CLL cells were stimulated via the SDF1-α-CD184 signalling pathway resulting in ZAP-70 phosphorylation. Its expression and phosphorylation was investigated alongside other prognostic factors and also correlated with B-CLL progression. More importantly, this study demonstrated that ZAP-70 positive cells are more responsive to signals derived from their surrounding environment, such as SDF-1α.

In conclusion ZAP-70, CD38, and CD23 expressions together with IgVH gene mutational status were confirmed as indicators of poor prognosis. Response to external stimuli by some B-CLL cells, resulting in ZAP-70 phosphorylation represents the most novel aspect of this thesis and demonstrates ZAP-70 involvement in B-CLL signalling. Additionally, raised NK: B-CLL and T: B-CLL cell ratios were identified as good modifiable variable predictors of time to treatment that could be used for monitoring and therapeutic purposes. Since B-CLL is an incurable disease, the identification of prognostic factors could help in deciding the best time for intervention in B-CLL patients.

Citation

Maramba, A. ZAP-70 Phosphorylation and other prognostic factors in adult B-chronic lymphocytic leukaemia patients. (Thesis). University of the West of England. Retrieved from https://uwe-repository.worktribe.com/output/931681

Thesis Type Thesis
Deposit Date May 30, 2013
Publicly Available Date Mar 28, 2024
Keywords leukaemia, cancer
Public URL https://uwe-repository.worktribe.com/output/931681
Award Date May 29, 2013

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