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http://hdl.handle.net/11375/26374
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DC Field | Value | Language |
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dc.contributor.advisor | Bhatia, Mick | - |
dc.contributor.author | Markous, Gena | - |
dc.date.accessioned | 2021-04-30T13:34:07Z | - |
dc.date.available | 2021-04-30T13:34:07Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | http://hdl.handle.net/11375/26374 | - |
dc.description.abstract | Acute myeloid leukemia (AML) is an aggressive cancer that begins in the rare blood-forming stem cell subpopulation of the bone marrow, in which the ability to produce functionally specialized, mature blood cells becomes impaired. The prognosis for patients with AML is vastly grim due to a low survival rate, rapid onset, and limited, non-curative treatment options. The understanding of how healthy blood cells progress to lethal leukemic cells is lacking, making it difficult to identify biological predictors and develop novel therapeutics. However, an intermediate state termed myelodysplastic syndrome (MDS) from healthy hematopoiesis provides an opportunity to unravel the mechanisms involved in the initiation and progression of this disease to AML. Much like other cancers, the accumulation of gene mutations in blood-forming stem cells is the driving force behind initial malignancy of this tissue. Recent studies have shown that many of those recurrent mutations are directly related to abnormal DNA methylation, a type of epigenetic modification, that alters gene expression resulting in aberrant cell development. To investigate this, we have taken advantage of our previously described in vivo mouse model of MDS-to-AML transition, governed by induced genetic mutation of GSK3, and have developed an in vitro system that uniquely allows for the selection, growth, and expansion of the rare blood cells responsible for initiating disease. Here, our in vitro system has brought to light specific phenotypes that could be the culprits of early transformation and a platform to explore causal genetic and epigenetic factors that govern disease progression. I propose that the system presented in this thesis serves as a surrogate that mimics MDS-to-AML transition and can be used to perform causal experimental studies. The overarching goal is to move the field forward by identifying tangible targets that have therapeutic intervention or predictive biomarker potential. | en_US |
dc.language.iso | en | en_US |
dc.title | A Surrogate In Vitro System to Define Initiating Events of MDS and Transition to AML Disease | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Biochemistry and Biomedical Sciences | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Markous_Gena_2021April_MSc.pdf | 19.68 MB | Adobe PDF | View/Open |
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