Unraveling the Mechanisms of Inherited Predisposition to Childhood Leukemia
Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and a major cause of death from disease in this age group. Despite the possibility of a cure, ALL treatments can lead to significant health problems later on. Early detection and understanding of ALL could greatly reduce the impact of cancer in children. Many genetic factors have been identified that increase the risk of developing a specific type of ALL called B-cell ALL, but how these factors contribute to the disease is still not fully understood. Recent studies have begun to uncover how these genetic risks are linked to certain B cell precursors, yet the exact way these genetic variants affect the disease process is unclear. We hypothesize that these genetic differences might hinder the normal development of B cells and thereby increase the likelihood of acquiring mutations that can lead to cancer. Our proposal aims to delve into how these genetic variants affect B cell development and behavior, which could lead to new ways to predict, prevent, and treat this type of leukemia.
Project Goal:
Our project seeks to unravel the genetic underpinnings of B-cell Acute Lymphoblastic Leukemia (B-ALL), a prevalent childhood cancer, with the ultimate goal of paving the way for new preventive and treatment strategies. Our approach in this proposal is twofold. First, we will use a novel system we have developed to mimic the process of B cell development from human blood stem cells, allowing us to introduce specific genetic changes known to increase B-ALL risk. By examining how these changes affect cell development and gene regulation, we aim to understand how they contribute to leukemia onset. Second, we will investigate how alterations in two regulators of gene expression, PAX5 and EBF1, which are known to be associated with B-ALL risk, affect the cellular machinery at a detailed level using cutting-edge genomic techniques. This comprehensive study is designed to shed light on the complex genetic factors that predispose individuals to B-ALL, with the hope of identifying targets for future interventions to prevent or treat this challenging disease.
