The role of ZMIZ1-relapsed enriched mutations in pediatric acute lymphoblastic leukemia
Mentor Name: Bill Carroll
While survival for acute lymphoblastic leukemia (ALL) has improved throughout the years, approaching 90%, up to 20% of children relapse. Understanding why certain patients relapse or become refractory to therapy is important to improve overall survival. We and others have shown that a small number of leukemia cells acquire certain mutations that allow them to resist one or more agents use in treatment. We now aim to investigate recently discovered novel mutations found in the gene ZMIZ1 specifically at relapse in samples from patients on treatment. Our first goal is to explore the role of mutations in ZMIZ1 in promoting relapse by creating cell lines engineered to express the mutant or normal form of ZMIZ1 and testing their impact on cell growth and survival after exposure to different chemotherapeutic agents. Our second goal is to discover how ZMIZ1 mutations alter expression of other genes and signaling pathways by determining interactions of mutant ZMIZ1 with gene regulatory regions and genes up or down regulated in the presence of the mutant compared to the normal ZMIZ1. Our approach could identify another potential driver of drug-resistance, ZMIZ1, that could serve as a novel target for treatment strategies.
