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Master's Thesis - Abigail Beer.pdf (593.98 KB)

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Development of an Inducible c-MYC Murine Model

Beer, Abigail J
http://rave.ohiolink.edu/etdc/view?acc_num=osu1602754882137456

Abstract Details

2020, Master of Science, Ohio State University, Molecular, Cellular and Developmental Biology.
Chronic lymphocytic leukemia (CLL) is a common leukemia that affects over 20,000 people and is caused by an accumulation of malignant mature B cells in the blood, bone marrow, and secondary lymphoid tissues. In recent years, treatment options have increased significantly and knowledge of the pathways involved in the disease has advanced substantially. However, about 10 percent of patients with CLL develop Richter transformation (RT), a condition where patients with CLL develop an aggressive secondary lymphoma. This condition is characterized by a poor clinical course with short survival times. Although RT is well defined, there is currently not much known about the genetic and epigenetic changes that occur during the development of the lymphoma. One factor that contributes to this lack of knowledge is the limited number of animal models and cell lines available to study RT. Currently, there are no Richter transformation cell lines and only a few animal models that demonstrate a Richter like disease. One of these murine models was recently developed in our lab and has been shown to model an aggressive leukemia and lymphoma. Due to the lack of models to study RT, our lab is aiming to establish a novel murine line that recapitulates all stages of RT. We have started developing this model by creating a TCL1 mouse that has B-cell specific inducible c-MYC overactivity. In RT, c-MYC deregulation is common and occurs in approximately half of all cases, and the TCL1 model is a well-established CLL murine model. Temporal and spatial regulation of c-MYC overactivity will allow us to study the genetic and epigenetic changes that occur during development of the secondary lymphoma. This murine model will better recapitulate the disease progression that is seen in patients with RT and will allow us to study transformation for the first time. Characterization of this model will be required in order to establish it as a reliable and available method to aid in furthering our understanding of RT. Once established as a reliable model to study RT, our lab will utilize the murine model to test targeted therapies against Richter transformation. The treatment options currently available for RT result in low percentages of response and short survival times. Through this work, we will have a better murine model to study Richter transformation.
Rosa Lapalombella, Dr. (Advisor)
Jennifer Woyach, Dr. (Committee Member)
Amanda Toland, Dr. (Committee Member)
Molecular Biology

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Citations

  • Beer, A. J. (2020). Development of an Inducible c-MYC Murine Model [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1602754882137456

    APA Style (7th edition)

  • Beer, Abigail. Development of an Inducible c-MYC Murine Model. 2020. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1602754882137456.

    MLA Style (8th edition)

  • Beer, Abigail. "Development of an Inducible c-MYC Murine Model." Master's thesis, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1602754882137456

    Chicago Manual of Style (17th edition)

osu1602754882137456
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