Defining the Phenotypic and Biological Impact of IKZF1 Deletions in Pediatric B Cell Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and despite our best therapy up to 20% of children with ALL will not be cured. Therefore, it is important to identify which patients are at risk for a poor outcome and to find ways to better treat these patients. A gene called IKZF1 is altered in 20-30% of pediatric ALL patients. Patients with IKZF1 abnormalities have a particularly poor outcome, indicating this is a group of patients is greatly in need of new treatment strategies. While we know that IKZF1 abnormalities are important in ALL, we do not fully understand how they contribute to leukemia development nor if clinical and biological differences exist between the different types of IKZF1 abnormalities. Our overarching aim is to address these prominent gaps in knowledge to ultimately improve the outcomes of this large subset of pediatric ALL patients.
We will apply cutting-edge CRISPR/Cas9 gene editing technology to create human leukemia cells with specific IKZF1 abnormalities commonly found in pediatric ALL. We’ll use these cells to study the impact of IKZF1 anomalies on the aggressiveness, sensitivity to chemotherapy drugs and the underlying biology of the specific IKZF1 abnormalities in ALL. In all, this work could facilitate improved prognostication of a large subset of ALL patients and identify potential therapeutic targets for future exploration.