Investigating the Role of TP53 in Peripheral T-Cell Lymphoma-GATA3 Subtype

Author

Zaina W. Nasser, University of Nebraska - Lincoln, University of Nebraska Medical CenterFollow
Dylan T. Jochum, University of Nebraska Medical CenterFollow
Waseem G. Lone, University of Nebraska Medical CenterFollow
Alyssa C. Bouska, University of Nebraska Medical CenterFollow
Sunandini Sharma, University of Nebraska Medical CenterFollow
Javeed Iqbal, University of Nebraska Medical CenterFollow

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Presentation date

Summer 8-10-2023

College, Institute, or Department

Pathology and Microbiology

Faculty Mentor

Dr. Javeed Iqbal

Research Mentor

Dylan Jochum

Abstract

Introduction: Non-Hodgkin Lymphoma (NHL) accounts for 4.1% of all cancers in the United States. Peripheral T-Cell Lymphoma (PTCL) consists of ~10-15% of all NHL in the Western world. 30-50% of these PTCLs are not classifiable/diagnosed and are instead designated as PTCL-Not Otherwise Specified (PTCL-NOS). The two major molecular subgroups within PTCL-NOS are PTCL-TBX21 and PTCL-GATA3, determined by their distinct T-helper (TH) transcriptional programs. GATA3 and TBX21 are the master-transcriptional regulators of TH2- and TH1-cell differentiation, respectively. The overall survival analysis of PTCL-NOS cases illustrates the clinical outcome of PTCL-GATA3 cases are significantly lower than PTCL-TBX21 cases over a broad timeframe. Thus, the need for understanding the underlying mechanism and finding therapeutic targets is at the utmost importance.

Background: TP53 mutations and/or TP53 loss deletions are frequent in PTCL-GATA3 cases, compared to PTCL-TBX21. TP53 is a protein that is essential in cycle regulation but also acts as a tumor suppressor. It stops cells from dividing if they have mutated or damaged DNA. Due to the high mutation rates observed in this subtype, we believe TP53 could play a major role in this mechanism. Therefore, it was important to focus on the TP53-GATA3 interaction at the genomic level. Prior studies using chromatin immunoprecipitation (ChIP)-qPCR on the intron 3 full GATA3 region suggested there was more TP53 binding in this intron region compared to other regions. Therefore, we designed a research strategy to determine the specific binding regions of TP53-GATA3 interaction and the function of the TP53 binding.

Keywords

Lymphoma, PTCL, GATA3, TP53, T-cell, intron, luciferase, chromatin immunoprecipitation

Recommended Citation

Nasser, Zaina W.; Jochum, Dylan T.; Lone, Waseem G.; Bouska, Alyssa C.; Sharma, Sunandini; and Iqbal, Javeed, "Investigating the Role of TP53 in Peripheral T-Cell Lymphoma-GATA3 Subtype" (2023). Posters: 2023 Summer Undergraduate Research Program. 4.
https://digitalcommons.unmc.edu/surp2023/4