Role of XIAP and TAL1 in t-cell acute lymphoblastic leukemia chemotherapeutic resistance

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Authors
Klahn, Joseph T.
Advisor
Olesen, James B.
Issue Date
2019-12-14
Keyword
Degree
Thesis (M.S.)
Department
Department of Biology
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Abstract

T-cell acute lymphoblastic leukemia (T-ALL) accounts for 15-25% of all acute lymphoblastic leukemia cases, with an estimated 5,960 new cases in the United States in 2018. T-ALL patients have a 68.1% survival rate, yet treatment options are limited. T ALL cells resist chemotherapy treatments and the cellular mechanism behind this resistance is largely unknown. One protein that may be involved in this resistance is T cell acute lymphocytic leukemia protein 1 (TAL1), which is an ectopically expressed transcription factor in T-ALL. Additionally, X-linked inhibitor of apoptosis (XIAP) is a protein that may play a role in the malignant progression by preventing apoptosis. XIAP has been shown to be a prognostic factor in multiple other cancers such as breast cancer, colorectal cancer, and thyroid cancer, but not much is known of its role in leukemia. It has been suggested that these proteins may display altered expression levels, but it is unknown if they are involved in the resistance to chemotherapeutic drug treatments, a common characteristic of T-ALL. This research showed that both XIAP and TAL1 have altered expression levels after western blot quantification, and because of this result, the effect of silencing both XIAP and TAL1 was investigated. Cell viability after XIAP silencing was analyzed via immunofluorescence and showed that knockdown of XIAP increased sensitivity to etoposide treatment in Jurkat cells. XIAP expression was evaluated after TAL1 silencing by both western blot and flow cytometry analysis, and the results indicated that XIAP expression correlates with TAL1 expression, suggesting a relationship between TAL1 and XIAP. Classifying the oncogenic activity of TAL1 has been relatively under-researched thus far, and this research shows a potential relationship between TAL1 and XIAP which could be driving resistance to chemotherapeutic drug treatments.

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