Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 54 for “"Acute myeloid leukaemia"”.
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The Mechanisms of HOXA9-mediated Acute Myeloid Leukaemia Maintenance
Acute myeloid leukaemia (AML) is an aggressive haematological malignancy, which, despite recent advances in treatment, results in only 50% long-term survival for the younger and lower than 10% for the older patients. Understanding the molecular mechanisms underlying leukaemogenesis and leukaemia …
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Defining the Epigenetic Evolutionary Dynamics that Precede Acute Myeloid Leukaemia
… by the acquisition of somatic driver mutations. Acute Myeloid Leukaemia (AML) is a good model system with which to address these questions. As well as the ease of sampling blood, mutations in epigenetic modifiers are some of the earliest and most common driver events in AML. In this work, we used …
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The role of non-genetic variability in Acute Myeloid Leukaemia
Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells with a dismal survival. It has a strong reliance on epigenetic and transcriptional factors for disease progression. Accordingly, my lab has previously identified KAT2A, a histone acetyl-transferase, …
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Molecular Characterisation and Therapeutic Targeting of NPM1-mutant Acute Myeloid Leukaemia
Mutations in the NPM1 gene are found in 30% of acute myeloid leukaemia (AML) cases. Despite their prevalence, the molecular consequences of NPM1 mutations (NPM1c) are incompletely understood and this hinders progress in designing effective therapeutic strategies. This thesis describes my work to …
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Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa
… molecular landscape of cytogenetically normal acute myeloid leukaemia (CN-AML) renders it an ongoing therapeutic challenge worldwide. The latest European LeukaemiaNet (ELN) 2017 guidelines attempt to address this by guiding post-remission therapy according to six prognostically informative …
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DNA repair deficiencies as a biomarker for treatment response in acute myeloid leukaemia
Acute Myeloid Leukemia is most commonly seen in people over the age of 65. Globally, there is an increasingly elderly population so the rate of incidence of AML is set to increase. The therapy landscape for AML has changed little over the past four decades. Cytarabine, first approved in 1969, is …
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A study of the NF-κB signalling pathway in human acute myeloid leukaemia.
… Constitutive NF-κB signalling occurs within acute myeloid leukaemia cells, promoting cell survival. This provides reason to investigate the NF-κB signalling pathway in greater detail. Prevention of NF-κB signalling should lead to cell apoptosis of AML cells but this outcome may be affected by …
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The Role of EZH2 in the Induction and Maintenance of Acute Myeloid Leukaemia
… while loss-of-function mutations are found in myeloid malignancies. This thesis is a study of this apparent contradiction, examining the importance of cellular context for Ezh2 loss during the evolution of a single malignancy, Acute Myeloid Leukaemia (AML). This work demonstrates diametrically …
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The evolutionary dynamics of clonal haematopoiesis and its progression to acute myeloid leukaemia
Acute myeloid leukaemia (AML) is an aggressive blood cancer which claims the lives of 70-80% of patients within 5 years of diagnosis. Like many other cancers, AML usually develops as a consequence of serial acquisition of somatic driver mutations; a process that starts many years, or even decades, …
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Characterization of chromosomal abnormalities in acute myeloid leukaemia patients at the university teaching hospital, Lusaka, Zambia
Acute myeloid leukaemia (AML) is a highly malignant clonal hematopoietic disease caused by both inherited and acquired genetic alterations. Current AML classification and prognostic systems incorporate genetic information but are limited to known abnormalities that have previously been identified …
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Characterization of chromosomal abnormalities in acute myeloid leukaemia patients at the university teaching hospital, Lusaka, Zambia
Acute myeloid leukaemia (AML) is a highly malignant clonal hematopoietic disease caused by both inherited and acquired genetic alterations. Current AML classification and prognostic systems incorporate genetic information but are limited to known abnormalities that have previously been identified …
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Identification and characterisation of Pu.1-driven gene regulatory complexes and networks in Acute Myeloid Leukaemia.
… and differentiation of both mature lymphoid and myeloid cells. The dysregulation of key haematopoietic transcription factors, including PU.1, is a cardinal feature of acute myeloid leukaemia (AML) and PU.1 is either deleted or mutated at low frequency in AML, suggesting it as a tumour suppressor. …
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Identification of novel genetic vulnerabilities and therapeutic targets in acute myeloid leukaemia using CRISPR dropout screens
Acute myeloid leukaemia (AML) is an aggressive cancer with a poor prognosis, for which mainstream treatments have not changed for decades. To identify novel therapeutic targets in AML, I have optimized a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening …
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Investigating the metabolic impact of Metformin and Berberine in combination with Venetoclax for Acute Myeloid Leukaemia treatment
Acute myeloid leukaemia (AML) stands as a significant challenge in haematological malignancies, particularly due to poor outcomes in older patients and resistance to therapy. BCL-2, an anti-apoptotic protein, is overexpressed in AML. The BCL-2 antagonist Venetoclax inhibits OXPHOS and induces …
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The impact of chronic loss of STAG2 on DNA damage repair and the epigenome in acute myeloid leukaemia
Acute myeloid leukaemia (AML) is a genetically heterogeneous disease characterised by the expansion of immature blast cells in the bone marrow and it primarily affects individuals aged 65 and over. Through next generation sequencing studies, the genetic landscape of AML has become increasingly …
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The development of a flow cytometric method to detect the presence of mutated nucleophosmin in Acute Myeloid Leukaemia
… Health Organisation (2008) classification of Acute Myeloid Leukaemia with recurrent genetic abnormalities. Current methodology uses reverse transcriptase polymerase chain reaction (RT-PCR) and genomic deoxyribonucleic acid (DNA) PCR techniques to detect NPM1 DIM. Although these methods are …
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Doxorubicin combined with phytochemicals as pro-apoptotic agents and protein kinase inhibitors for the treatment of acute myeloid leukaemia
Acute myeloid leukaemia is one of the most common form of adult leukaemia with several kinase mutations. The FLT3-ITD mutation is a common kinase mutation observed in (20-30%) of AML patients and this mutation is also the most involved in the prognosis of AML. It confers poor treatment outcome in …
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