Funded by the Dick Vitale Gala, in memory of Benji Gilkey
T-cell acute lymphoblastic leukemia is an aggressive cancer that is most common in teenagers. Many patients cannot be cured, even with intensive chemotherapy. Our goals are to understand why chemotherapy does not cure some patients, and use this knowledge to improve treatment. We found that chemotherapy cannot cure patients whose leukemia cells are very difficult to kill in a test called BH3 profiling. This proposal is focused on mutations of a gene called JAK3 as a cause of death resistance of leukemia cells. This idea could be immediately translated into a clinical trial because JAK3-blocking drugs are already FDA-approved for clinical use. Here, we will ask the following questions: 1) Do JAK3 mutations block cell death in leukemia cells? 2) Will a JAK3-blocking drug improve the effectiveness of chemotherapy? 3) Is a JAK3-blocking drug safe and effective for the treatment of children with T-cell acute lymphoblastic leukemia? Successful completion of this project could lead to more effective treatment options for children with this particularly high-risk subset of T-cell leukemia.