Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Normal blood cell production is maintained by rare immature cells that reside in the bone marrow. These are the cells that become transformed to give rise to leukemia which is a cancer of the blood. Many forms of leukemia are still not effectively treatable and are therefore fatal within a few years. Unfortunately we know very little about how these leukemias develop and why they are so resistant to therapy. In addition, methods that produce mouse leukemias do not generate diseases that closely resemble human leukemias. Therefore models that would allow to study the initiation and progression of leukemia directly in human cells are needed. The objective of my project is to create and study such a model of a human leukemia by introducing a mutant gene into normal human cells and cells that are pre-leukemic. In my preliminary experiments, I have already discovered that this can work and the altered cells produce an aggressive human leukemia when they are transplanted into mice that lack an immune system. I now propose to investigate the molecular changes that cause this generation of a leukemia in the targeted cells. My results should create a foundation for the future development of definitive curative strategies and also broaden our understanding of the behaviour of other cancers where the same mutant gene is active.