| The genetic underpinnings of a cancer are key to understanding the etiology of the disease and thus to providing a cure, because any robust cure of the disease will need to target a therapeutic window, a gene or a group of genes that are different between the cancerous cells and the normal cells. The research shown in this thesis gives insight into the genetic causes of acute myelogenous leukemia in an attempt to find a therapeutic window for this disease. A genetic screen using CRISPR-Cas9 is designed and conducted in a cell line designated RN 2-5 that was determined to recapitulate the acute myelogenous leukemia phenotype in culture and in a mouse model of the disease. Following up on the most important hits of this screen will very likely lead to important therapeutic targets. Two bioinformatics methods, a machine-learning algorithm and a statistical approach, are also used to identify key features of the expression of genes targeted in the screen. A combination of genetic screening and bioinformatics will have great efficacy in the future in finding genes differentially expressed, and differentially required, by cancer cells versus normal cells. |
