Date of Award

5-19-2019

Document Type

Honors Thesis

Department

Biochemistry & Molecular Biology

First Advisor

Michael Roberts

Language

English

Abstract

Acute Myeloid Leukemia (AML) is the most common form of leukemia in adults and while it has a high remission rate, relapse with therapy resistance is common, indicating the need for more targeted and effective therapies. It is possible to reprogram AML cells in culture to undergo cell cycle arrest, differentiation into “normal” macrophage-like cells, and apoptosis using phorbol 12-myristate 13-acetate (PMA), a diacyl glycerol (DAG) mimic. While this is effective in “curing” leukemia in culture, PMA is too toxic to serve as a therapy in AML patients. During these PMA-induced changes, approximately 1250 genes change in expression. The goal of this study was to see if the genes Fos and JunB, which are highly upregulated post PMA treatment, are responsible for portions of the genetic reprogramming mediating these phenotypic changes. These genes are transcription factors and members of the AP-1 complex, which is known to play a role in regulating the cell cycle, differentiation and programmed cell death. In this study we show that Fos and JunB are capable of initiating specific responses by overexpressing them individually or together via transfection in the AML cell line, HL-60.

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