CHOP hematologist Stella T. Chou, MD, received a $100,000 Springboard Grant from Alex's Lemonade Stand Foundation 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.

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. Using iPSCs as the stepping stones, researchers will follow the pathways of aberrant blood formation and create a timeline of the progression to leukemia associated with Down syndrome.

In response to the budget reductions at the National Institutes of Health, Alex's Lemonade Stand Foundation stepped in to advance new projects with high impact potential, such as Dr. Chou's investigation.

"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," stated Jay Scott, co-executive director of the foundation, in a press release.