Studies of the Wnt/Beta-catenin signalling pathway in chronic myeloid leukaemia



Fowler, Rachael
Studies of the Wnt/Beta-catenin signalling pathway in chronic myeloid leukaemia. PhD thesis, University of Liverpool.

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Abstract

The Wnt/β-catenin signalling pathway is involved in regulating cellular transcription of numerous target genes in chronic myeloid leukaemia (CML). A previous report using granulocyte-macrophage progenitors (GMPs) showed that elevated levels of unphosphorylated (active) β-catenin, alongside mis-splicing of glycogen synthase kinase 3β (GSK3β), correlated with disease progression. It was of interest to determine if using the more readily available peripheral blood mononuclear cells (MNCs) also showed any correlation with patient outcome when β-catenin and GSK3β were measured in this source material. Further investigation in these cells addressed GSK3β activity regulation, possible regulation of c-Myc degradation by GSK3β, and investigation of Wnt transcription factors in CML. Results indicated that levels of β-catenin (and its phosphorylated variants) could not be used to distinguish patient treatment outcomes using CML MNCs. However the levels of BCR-ABL1 induced β-catenin-Tyr654 phosphorylation showed a significant decrease in patients in blast crisis compared to chronic phase (P=0.012), as did the levels of GSK3β – which demonstrated significantly decreased activity in blast crisis patients via a significant increase in Ser9 phosphorylation and a significant decrease in Tyr216 phosphorylation in blast crisis compared to chronic phase (P=0.026 and

Item Type: Thesis (PhD)
Additional Information: Date: 2014-08 (completed)
Subjects: ?? RC0254 ??
Depositing User: Symplectic Admin
Date Deposited: 20 Aug 2015 15:33
Last Modified: 17 Dec 2022 01:31
DOI: 10.17638/02007740
URI: https://livrepository.liverpool.ac.uk/id/eprint/2007740