Acute myeloid leukemia (AML) is a hematological cancer that results in uncontrolled proliferation of non-functional neoplastic myeloid blasts. Refractory disease is a primary reason as to why AML patients are difficult to treat. Despite extensive studies on AML, minimal progress has been made in the development of effective therapies. Our lab has previously proven that blood vessels are sanctuary sites for AML, and that new therapies need to be developed to target these post-chemotherapy refractory cells. We screened 31 million compounds using a high throughput screening assay that mimics the AML cells sequestered in the chemo-protective vascular niche and found a hit that selectively killed AML cells and spared bone-marrow derived endothelial cells. We discovered that this compound targeted an important splicing factor, and thereby modulating the splicing landscape. We specifically identified a key oncogene that was alternatively spliced resulting in AML cell death. My project is focused on validating the mRNA splicing patterns that are regulated by our target to potentially develop a novel therapeutic strategy.