FA confers a high risk of developing leukemia at a young age, and patients with FA who develop leukemia are difficult to treat with have poor long-term outcomes. Leukemia develops as a consequence of the acquisition of genetic mutations within blood stem cells in the bone marrow that cooperate to drive uncontrolled blood cell growth. Our understanding of the specific genetic mutations that occur in human FA blood cells to drive leukemia is poor due to the lack of disease models. We have developed a system to reproducibly generate large numbers of human FA blood stem cells that we will use to determine the key genetic mutations that drive the development of leukemia. Identification of these collaborating mutations may lead to improvement in screening for and treating blood cancers in FA.