While survival rates of children with acute lymphoblastic leukemia (ALL) have improved greatly over the last decades, successful treatment of infants (<1 year of age) diagnosed with MLL-rearranged ALL remains very challenging. These patients frequently relapse, typically while still on treatment, after which they often fail to respond to therapy. Hence, there is an urgent need to develop novel and more effective treatment options for this group of high-risk patients. Within this project, we aim to establish accurate preclinical models to validate and study the efficacy of promising novel therapeutic agents that were previously identified within our group. Additionally, we will use these preclinical models to gain insight into the mechanisms underlying the development of therapy resistance against current therapeutics as well as our novel compounds. Together these approaches will help us develop innovative treatment strategies to enhance the survival chances of MLL-rearranged infant ALL patients, and identify potentially actionable targets for preventing or treating relapsed disease.