Inherited blood disorders and blood cancers are prevalent in the population. The advent of genetic diagnostics can help select the most promising treatment for each patient. However, we still do not know enough about how genetic information affects treatment outcomes. To help answer this question, we are using patient stem cells to create personalized models of blood disorders. We ‘enroll’ patients who present with more aggressive clinical disease, faster progression, and poor response to standard treatments. Stem cell lines from each patient are used to recreate disease ‘in a dish’. By correlating patient genetic testing with drug responses we can make predictions about mutations that ‘drive’ poor outcome. We then use gene editing to precisely test how individual mutations contribute to drug resistance. In particular mutations in a gene called TP53 are associated with poor prognosis in blood cancers. By demonstrating the molecular mechanisms by which TP53 mutations contribute to drug resistance will help us modify existing drug regimens or develop new treatment options for these patients.