Over the past 50 years, remarkable progress has been made in our understanding of the molecular genetics that underlie pediatric acute leukemia. This information has come from a variety of different lines of investigation, including cytogenetics and genomic sequencing efforts to identify the underlying lesions, as well as functional studies in cellular and murine model systems to characterize the biological consequences of the identified genetic alterations. The detailed understanding that has emerged from these studies has served as the foundation for efforts to individualize treatment so that each child with leukemia has the best possible chance for a cure.
Although our understanding of the landscape of somatic and germline mutations underlying acute leukemia has rapidly progressed, it remains incomplete. Moreover, why some patients respond to current therapeutic approaches and are cured, whereas others relapse and ultimately succumb to their disease remains a mystery. Fortunately, recent advancements in our ability to sequence leukemias at both a population and a single cell level are beginning to shed light on the diverse mechanisms that can lead to refractory disease. This lecture will focus on the progress that has been made over the last 15 years in advancing our understanding of pediatric acute leukemia and the impact this information is having on our ability to further increase cure rates.
James R. Downing, MD, was nominated for the E. Donnall Thomas Lecture and Prize based on a body of work related to the hematopathology and molecular biology of childhood leukemia, particularly acute lymphoblastic leukemia.