Assessing Pim-1 Kinase Inhibition as an Effective Treatment for Acute Myeloid Leukemia

Abstract

Proviral integration site for malignancy-1 (PIM-1) is a serine/threonine kinase proto-oncogene that has many important functions, namely cell proliferation and signal transduction, in the context of Acute Myeloid Leukemia (AML). Generally, PIM-1 kinase, which arises from the expression of the PIM-1 oncogene, can cause poor prognosis of AML. Additionally, PIM-1 kinase, also a substrate of Triad1, stabilizes as expression of Triad1 decreases during the prognosis of AML. Thus, this project looks at PIM-1 kinase inhibition and aims to determine its effectiveness in treatment for AML and how it can affect potential therapeutic interventions. AZD1208, a potent pan-PIM inhibitor, is theorized to be an alternative treatment for AML instead of chemotherapy. This project involves a luciferase reporter assay, which is used to track PIM-1’s gene activation. The assay allows for analyzing PIM-1s impact on signaling pathways and helping determine its oncogenic potential through measuring the fluorescent activity in the Pim-1 kinase promoter