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Title: Investigations into the pathogenesis of essential thrombocythemia
Author: Allen, Anthony John Robert
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2006
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Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder of unknown aetiology, characterized by sustained thrombocytosis and megakaryocyte hyperplasia. Three strategies were used to investigate disease pathology. Firstly, PCR-based assays using fluorescently labelled primers to measure X-chromosome inactivation patterns were evaluated and clonality status shown to be stable in 14 patients with polyclonal and 8 patients with clonal myelopoiesis studied over a median of 54 months (range 10-102) and 52 months (range 5-97) respectively. Secondly, mutations and polymorphisms in cytokines implicated in thrombopoiesis were investigated in ET patients. No mutations in the 5' untranslated region of the thrombopoietin gene, previously described in hereditary thrombocythaemia, were found. Genotypes and gene frequencies for polymorphisms previously shown to affect circulating cytokine levels in the transforming growth factor pi and interleukin-6 genes did not differ between patients and controls. Thirdly, representational difference analysis was used to compare global gene expression in platelet mRNA from an ET patient with monoclonal myelopoiesis with that from a normal control. Three genes were identified as differentially expressed: RANTES, CD32 (FcylIRA), and FLP. CD32 expression was further investigated using a multiplex semi-quantitative RT-PCR assay. Platelet CD32 expression was increased in 52 ET patients compared to normal controls (median CD32:GAPDH ratio 21, range 2-73 and 1, range
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available