Trim24 In Normal & Malignant Hematopoiesis

<p>Treatment for acute myeloid leukemia (AML) has changed little in the past four decades. For the majority of AML patients, current treatment options include chemotherapy and allogeneic stem cell transplants, which also involves high-dose chemotherapy or radiation treatment. These options have little success in the long-run, as only an estimated 26% of patients survive five years post-diagnosis. In efforts to address this low survival rate, interest has increased for targeting epigenetic pathways in AML. This focus stems from the discovery that AML is frequently driven by blockades on hematopoietic stem cell differentiation, which involves a series of coordinated epigenetic changes. Given its reported roles as an epigenetic reader, stem cell regulator, and known oncogene, we investigated <em>TRIM24</em> for putative relevance in AML. Expression data from previous studies have also suggested roles for <em>TRIM24</em> in chronic myeloid leukemia and acute lymphocytic leukemia; however, no studies to date have reported measurements of <em>TRIM24</em> in AML from an <em>in</em> <em>vivo</em> system. Here, we report that low <em>TRIM24</em> mRNA expression in human AML patients (in TCGA) correlates with poor survival. Additionally, this association was found to be independent of gene expression signatures of prognostic significance, such as Gentles leukemic stem cell signature. Furthermore, loss of <em>Trim24</em> in murine, <em>MLL</em>-<em>AF9</em>-driven AML worsened survival and increased leukemic stem cell numbers, while having no observed effects on normal hematopoiesis. These results lay the groundwork for future investigations of the role of <em>TRIM24</em> in AML, which has the potential to aid development of novel therapeutic strategies.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2018

Authors dc:creator

• Shaw, Justin
• <p>https://orcid.org/0000-0001-7166-1322</p>

Contributors dc:contributor

• Margarida Santos
• Michelle Barton
• Xiaobing Shi

• Leukemia
• AML
• Hematopoiesis
• Hematopoietic
• Stem cell
• MLL
• MLL-fusion
• MLL-AF9
• Cancer Biology
• Molecular Genetics

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/833

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1878