One in every 691 babies in the U.S. is born with Down syndrome, according to the National Down Syndrome Society, and have a predisposition for a certain kind of cancer. A Children’s Hospital hematologist, Stella T. Chou, MD, will receive $100,000 over the course of one year to fund her research on how an extra chromosome 21 and mutations in a transcription factor gene called GATA1 affect blood development, creating a predisposition to leukemia in children with Down syndrome.
For fiscal year 2013, the sequestration required NIH to cut 5 percent or $1.55 billion of its budget. In response to the budget reduction, Alex’s Lemonade Stand Foundation stepped in to advance new projects with high impact potential, such as Dr. Chou’s investigation.
“With less than 5 percent of the federal government’s total funding for cancer research each year being dedicated to childhood cancers, Alex’s Lemonade Stand Foundation is dedicated to keeping promising research alive,” stated Jay Scott, co-executive director of the foundation, in a Dec. 19 press release announcing the award. “Through the Springboard Grant, we work to sustain the research of these promising investigators while they reapply for large-scale funding, ultimately resulting in better treatments and cures for all childhood cancers.”
Dr. Chou’s research project aims to “provide new insights into blood cell production, generate new experimental tools for the biomedical community, and elucidate new strategies to study inherited blood diseases.”
Children with Down syndrome are predisposed to “a unique constellation of blood diseases,” Dr. Chou said. These include an increase in total red blood cell mass and a decrease in the number of platelets. In addition, about 10 percent of neonates with Down syndrome are born with preleukemia known as transient myeloproliferative disorder (TMD), which spontaneously resolves in most cases. However, 20 percent of patients with TMD subsequently develop acute megakaryoblastic leukemia (AMKL) by age 5, which responds well to chemotherapy but is associated with significant treatment-related toxicity.
In order to figure out how TMD and AMKL occur, Dr. Chou’s research team will trace the formation and development of blood cells from their early beginnings during embryogenesis and then define how they go awry. They will focus on how two potential culprits — mutations in GATA1 and genes on chromosome 21 (HSA21) — act separately and together to modulate hematopoiesis.
The investigators will use a novel approach that involves the creation and manipulation of patient-derived induced pluripotent stem cells (iPSCs) for the study of genetic disease. iPSCs are a renewable human cell source that can recapitulate the multiple stages of blood formation. They are an alternative to human samples, which are difficult to obtain in sufficient quantities for scientific investigation.
Cancer is the leading cause of death by disease among U.S. children between infancy and age 14, according to the National Cancer Institute. Approximately 11,600 new cases of pediatric cancer are expected to be diagnosed in children ages 0 to 14 years in 2013. Alex’s Lemonade Stand Foundation has raised more than $65 million toward finding a cure for all children with cancer, funding more than 350 pediatric cancer research projects nationally.