HMGA1 in therapy resistant leukemia
Mentor Name: Linda Resar
Childhood leukemias are comprised of two major subtypes: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Pediatric leukemias are frequently caused by mutations in blood stem cells that disrupt normal growth and differentiation. One form of childhood AML, called KMT2A-r AML, is caused by a fusion of the KMT2A gene (formerly MLL1) to another gene. Another form of pediatric leukemia, called acute megakaryocytic leukemia (AMKL), occurs in children between the ages of 1 and 3 years and can express a splice variant in the MPL gene. Both KMT2A-r AML and AMKL are associated with therapeutic resistance and poor outcomes. Our research team focuses on the High Mobility Group A1 (HMGA1) chromatin regulator in pediatric leukemia. We previously discovered that diverse gene mutations associated with relapse converge on HMGA1, allowing leukemic cells to expand and resist therapy. We are now pursuing studies to uncover pathways underlying therapy-resistant leukemia cells with the goal of designing effective therapies for children with aggressive disease. The goals of this project are: 1) to investigate the role of HMGA1 in mediating therapeutic resistance in KMT2A-r AML and AMKL, and 2) to identify new approaches to treat these refractory leukemias.
