Wang, Yuyin
(2024)
Title Page
Investigating the role of NFAT transcription factors in acute lymphoblastic leukemia.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers originating in the bone marrow. Personalized therapy targeting specific high-risk ALL subtypes can significantly improve treatment outcomes. The nuclear factor of activated T cells (NFAT) can potentially be a therapeutic target in ALL. NFATs are transcription factors that play crucial roles in lymphocyte regulation and have been implicated in various cancers, including breast cancer, other leukemias, and so on. However, their roles in ALL remain unclear. We hypothesize that ALL cells have constitutively active NFATs, and inhibiting the transcriptional activity of NFATs can suppress the growth and proliferation of ALL. RNA-seq analysis of pediatric ALL patient samples identified various ALL subtypes with unfavorable prognosis and upregulated NFAT expression. Constitutive activation of NFAT in ALL cell lines was evaluated by a western blot of cytoplasmic and nuclear extract compared to normal human PBMCs (peripheral blood mononuclear cells). We show that pharmacological NFAT inhibition in ALL cell lines resulted in reduced cell proliferation, which correlated with the NFAT expression of the cells. ALL murine models were used to assess the translational potential of NFAT inhibition in vivo.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
7 August 2024 |
| Date Type: |
Publication |
| Defense Date: |
29 May 2024 |
| Approval Date: |
7 August 2024 |
| Submission Date: |
9 July 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
49 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Acute lymphoblastic leukemia (ALL); Nuclear factor of activated T cells (NFAT); Transcription factors; Target therapy |
| Date Deposited: |
07 Aug 2024 12:18 |
| Last Modified: |
07 Aug 2024 12:18 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46663 |
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