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 36 for “"Acute myeloid leukaemia (AML)"”.
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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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MANIPULATING CELL STATES FOR LEUKAEMIA DIFFERENTIATION THERAPY USING NETWORK PHARMACOLOGY
Acute myeloid leukaemia (AML) is a rapidly fatal blood cancer which is characterized by the accumulation of immature myeloid cells in the blood and bone marrow as a result of blocked differentiation. In this proof-of-concept study, we demonstrate a novel utility of the MOGRIFY® algorithm in …
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Investigating the translational and metabolic reprogramming of the bone marrow niche in myeloid malignancy
In acute myeloid leukaemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche was, until now, unclear. This study found that relapsing AML cells …
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Regulation of flt3 gene expression in haematopoietic and leukaemic stem cells
… key factor in enhanced survival and expansion in acute myeloid leukaemia (AML). Although there is extensive knowledge regarding mutations leading to the constitutive activation of Flt3 receptor activity, the molecular mechanisms underlying the regulation of the \(flt3\) gene in HSCs, and how such …
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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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Cholinergic signals promote the quiescence of normal or leukaemic stem cells through the activation of the α7-nicotinic receptor in bone marrow mesenchymal stromal cells
… after HSC transplantation in mice. In acute myeloid leukaemia (AML), cholinergic fibres are preserved despite a decrease in sympathetic noradrenergic innervation. Loss of sympathetic cholinergic innervation or α7 nicotinic acetylcholine receptor (α7nAChR) signalling in the BM …
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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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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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Antioxidant pathways and human leukaemia chemotherapeutic sensitivity
… eg imatinib has effectively eradicated chronic myeloid leukaemia (CML) morbidity. However, acute myeloid leukaemia (AML) remains essentially incurable for the vast majority of patients. The current gold-standard treatment for AML has remained relatively unchanged for decades, consisting of the …
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The human myeloproliferative disorders: molecular pathogenesis and clonal heterogeneity
… molecules and a variable tendency to develop acute myeloid leukaemia (AML). This thesis examined genotype-phenotype associations of JAK2 and MPL mutations, the presence of clonal diversity in the MPD and the genetic events associated with progressive disease. Mutations in MPL were identified …
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The pre-clinical evolution of haematological malignancies
… this process in the haematopoietic system, where leukaemia-associated mutations are detectable in >10% of individuals over the age of 50. This phenomenon, termed clonal haematopoiesis (CH), is associated with an increased risk of blood cancers, though only a small minority of individuals progress. …
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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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CRISPR AS A TOOL FOR TARGET DISCOVERY AND TECHNOLOGICAL INNOVATION: HIGH-THROUGHPUT CBE SCREENING TO EVALUATE M6A MODIFICATION PATHWAY IN CANCER PROLIFERATION AND DRUG RESISTANCE, AND INNOVATIVE PRIME EDITING STRATEGIES FOR DISEASE MODELLING AND THERAPY
… proliferation in colorectal cancer (CRC) and acute myeloid leukaemia (AML), and its downregulation by small molecule inhibitor affects proliferation in AML and is currently in phase I-II clinical trial. Therefore, expanding the study to all m6A effectors in cancer cell proliferation might be …
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Selezione e processazione di cellule Natural Killer da donatore aploidentico "KIR-ligand" incompatibile per l'immunoterapia adottiva di pazienti con Leucemia Acuta Mieloblastica ad alto rischio
… NK-mediated tumor cell killing, particularly in acute myeloid leukaemia (AML). Thirty-four high risk AML patients entered a phase I-II study of adoptive NK-cell based immunotherapy and were screened for the availability of one haploidentical KIR ligand mismatched donor. Thirteen of them resulted …
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The Role of Ribosomal Maturation Proteins WBSCR22 and EMG1 Methyltransferase Activity in Cancer
… of both methyltransferases has been reported in acute myeloid leukaemia (AML) and uveal melanoma (UVM), where it strongly correlates with poor prognosis. However, the specific role of these enzymes in cancer is still unknown. I identified both WBSCR22 and EMG1 catalytic activity as essential for …
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Interim analysis of Acute Myeloid Leukaemia treated on the Red Cross Children's Hospital Rx 2071 (adapted from the MRC AML 15 protocol)
Background: Due to the poor outcomes achieved in acute myeloid leukaemia (AML) treatment, the Red Cross War Memorial Children's Hospital (RCWMCH) Oncology service changed from a BFM-87 based protocol to one based on MRC-AML15 in 2007. Rationale: This study was designed to assess the outcomes and …
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Novel roles of KAT2A chromatin complexes ATAC and SAGA in normal and malignant haematopoiesis
… importance in malignant haematopoiesis such as leukaemia, given their reversible nature and potential for therapeutic targeting. Epigenetic histone modifiers are often found within large multi-subunit complexes, whereby their catalytic activity is exercised. However, very little is known about …
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Investigation of m6A-regulated RNA-binding proteins
… effects on RNA-binding proteins in MOLM-13, an acute myeloid leukaemia (AML) cell line. This was coupled with the OOPS quantitative proteomics technique to directly measure in the cell which RNA-proteins had their binding levels significantly altered by the loss of the modification. With this …
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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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