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 574 for “"Myeloid"”.
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Redox biology of myeloid leukaemias
Internal tandem duplication of FMS-like receptor tyrosine kinase (FLT3-ITD) has been associated with an aggressive AML phenotype. FLT3-ITD expressing cell lines have been shown to generate increased levels of reactive oxygen species (ROS) and DNA double strand breaks (dsbs). However, the molecular …
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Proteasome inhibition in chronic myeloid leukaemia
CML is treated effectively with TKI, however two key problems remain - the insensitivity of CM HSC to TKI and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and PI are cytotoxic against CML cell lines. We demonstrate that …
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Deciphering the Pathogenesis of Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a malignant disorder of the blood system. Hematopoietic stem cells (HSCs) supply and maintain this system by differentiating via intermediates into lineage-restricted progenitors that strongly proliferate to keep up with the high turn-over of mature blood cells. In …
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Treatment Response Prediction in Acute Myeloid Leukemia Patients
Predicting acute myeloid leukemia (AML) patient treatment response has the potential to impact clinical decisions. A prediction given at the time of diagnosis for treatment response can assist physicians in making effective treatment decisions and improving patient prognosis. This project aimed to …
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Characterization of human myeloid progenitors and their differentiation
… in commitment to either the lymphoid or the myeloid branch, in the latter followed by commitment to the neutrophil/monocyte and erythrocyte/megakaryocyte lineages. The objective of this thesis was to further characterize early human myeloid development. As a first step we established a map …
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Immunosuppressive Myeloid Cells in Breast Cancer and Sepsis
… towards a novel population of monocytic myeloid-derived suppressor cells (Mo-MDSCs). The gene-expression profile of cancer-derived monocytes was remarkably similar to that of reprogrammed immunosuppressive monocytes from patients with gram-negative sepsis. This suggests that Mo-MDSCs may …
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Regulation of Myeloid Leukemia Cells by Platelet Factor 4
… to be the main drivers of relapse in Acute Myeloid Leukemia. LSCs ability to retain key properties of healthy hematopoietic stem cells (HSCs) means they are quiescent, chemo-resistant, and able to repopulate eradicated leukemic blasts, making LSCs an important target in AML. However, their …
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NON-GENETIC MECHANISMS OF CHEMORESISTANCE IN ACUTE MYELOID LEUKEMIA
Acute Myeloid Leukemia (AML) is the most common type of acute hematological malignancy in adults. 40–60% of patients relapse due to the emergence of cellular resistance to anti- leukemic drugs. Drug resistance in leukemic cells has been associated with intratumoral heterogeneity, among which …
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Functional Modeling of Genes Upregulated in Chronic Myeloid Leukemia
Chronic myeloid leukemia (CML) is caused by the transformation of a primitive hematopoietic cell by the BCR/ABL1 fusion gene that is formed through the chromosomal translocation t(9;22). CML is currently successfully treated with tyrosine kinase inhibitors targeting the ABL1 kinase domain. However, …
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The Cell-Essentiality of KAT7 in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy, characterized by the uncontrolled proliferation and differentiation arrest of myeloid progenitors. Chemotherapy has been the front-line treatment for decades and cure remains elusive for the majority of AML patients. …
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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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Investigating the Therapeutic Potential of L-asparaginase in Myeloid Leukemia
Acute myeloid leukemia (AML) is a malignant disease of the bone marrow that results in the proliferation and accumulation of dysfunctional myeloid cells and the disruption of the normal hematopoietic process. The high rate of relapse and diversity of the disease at the genetic and epigenetic level …
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CELLULAR AND MOLECULAR MECHANISMS OF CHEMORESISTANCE IN ACUTE MYELOID LEUKEMIA
Acute Myeloid Leukemia (AML) remains an incurable disease, with a 5-year survival rate below 30%. While the introduction of new therapeutic approaches, such as targeted therapies and immunotherapy, has had a modest impact on AML prognosis, the standard treatment of AML is still based on …
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Defining the Epigenetic Evolutionary Dynamics that Precede Acute Myeloid Leukaemia
… 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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Long-term effects of imatinib on cognition in chronic myeloid leukaemia
… endorsed as a first line treatment for chronic myeloid leukaemia (CML) in the chronic, accelerated, and blastic phases. The survival advantage demonstrated by this target kinase inhibitor has meant that patients are now treated with this agent on a long-term basis. There is a growing literature …
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Targeting Apoptotic Pathways to Overcome Drug Resistance In Acute Myeloid Leukemia
… that BCL-2 protein is highly expressed in acute myeloid leukemia (AML) cells. BCL-2–specific inhibitor ABT-199 potently induces mitochondrial apoptosis in AML cells and effectively kills AML stem/progenitor cells. Our biomarker studies demonstrate that both BH3 profiling and the expression …
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Endogenous Mechanisms Regulating Myeloid Cell Mediated Inflammation During Acute Lung Injuries
… to limit excessive pulmonary inflammation in myeloid cells using a mouse model of sepsis-associated ALI. In the first approach we screened for microRNAs during the recovery phase of ALI that could potentially regulate inflammation. We found that miR-147 is highly expressed during the recovery …
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