Role of Proliferation in the Pathogenesis of T-cell Acute Lymphoblastic Leukemia
In spite of successful management of children with acute lymphoblastic leukemia (ALL), a fifth of diagnosed patients relapse after induction treatment. We propose to test the hypothesis that a deregulated response to childhood infections can induce expansion of pre-leukemic cells and overt leukemia. We previously described a gene that controls proliferation of T cells during homeostasis and following infection or vaccination. We plan to investigate whether gene deletion primes pre-leukemic cells to expand upon activation of the immune system and/or increases resistance of leukemia-initiating cells to chemodrugs. This project will provide a molecular framework to design adjunctive therapies in high-risk patients.