Linda Crnic Institute Lectures: “The Unique Clinical and Biological Features of Leukemias in Children with Down syndrome”
Jeffrey W. Taub, MD
Professor of Pediatrics, Wayne State University School of Medicine,
Division Chief of Oncology, Children’s Hospital of Michigan
March 7, 2012
Dr. Taub’s research has focused on studying the molecular epidemiology and pharmacology of childhood leukemia, the most common form of cancer in children and the leading cause of death from disease of American children. Using a unique source of blood samples collected at birth and used for genetic screening (“Guthrie cards”), his lab is screening for the presence of preleukemic clones (by PCR-based minimal residual disease assays) in the blood samples of children who subsequently developed leukemia. This would confirm a prenatal origin of leukemia and potential in utero exposures being linked to the development of leukemia. These studies are also examining factors including differences in folate metabolism which may account for the 2-3-fold higher incidence of acute lymphoblastic leukemia (ALL) in Caucasian compared to African American children in the United States. Another project in the laboratory is studying the biology of acute myeloid leukemia (AML) in children with Down syndrome. Children with Down syndrome have a 20-fold greater risk of developing leukemia compared to children without Down syndrome, and have the highest cure rate (80-100%) of any subgroup of AML patients. These studies use both primary clinical samples from patients diagnosed with AML, as well as clinically relevant leukemia cell lines, to examine the roles of both chromosome 21-localized and non-chromosome 21-localized genes in leukemogenesis and the metabolism of chemotherapy drugs. Findings from these studies are also being applied to developing new leukemia therapies in clinical trials for children without Down syndrome.