Meagan Vacek, DO, Pediatric Fellow, Hematology/Oncology/BMT, received a one-year, $44,034 Catalyst Grant from Alex’s Lemonade Stand Foundation for her project, “A Genomics Driven Pluripotent Stem Cell Model of Infant Lymphoblastic Leukemia.”
Acute lymphoblastic leukemia in infants (iALL) is a high-risk subtype of childhood leukemia. Most cases occur due to the rearrangement of the KMT2A (KMT2A-r) gene on chromosome 11q23. iALL originates in utero and is associated with chemotherapy resistance, early relapse, and rapid leukemic progression; all of which contribute to poor survival outcomes.
“Infants with this subtype of childhood leukemia have a dismal prognosis —only about one in three survive,” Dr. Vacek said. “Through our research, we expect to discover unique mechanisms of iALL emergence and progression. The long-term goal is to uncover specific targets for the development of new therapies for these patients.”
The KMT2A-r generates a driver fusion oncogene, most commonly KMT2A::AFF1, which transforms a normal white blood cell into a tumor cell. A collaborative team has created human induced pluripotent stem cell (iPSC) models with the oncogene KMT2A::AFF1. They will use the iPSC model to determine the genomic and epigenetic landscape and cellular evolution of this leukemia subtype.
The study has two aims:
- To use single cell genomics to investigate transcriptomic changes during hematopoietic differentiation of human iPSCs engineered to express the KMT2A:AFF1
- To compare the iPSCs to publicly available datasets on healthy human embryonic and fetal hematopoiesis
John Perry, PhD, Hematology/Oncology/BMT, is Dr. Vacek’s mentor for this project. Erin Guest, MD, Hematology/Oncology/BMT, and Jay Vivian, PhD, Clinical Genetics, provide additional guidance. This project is a collaborative transdisciplinary effort between Dr. Perry’s and Dr. Vivian’s labs and the University of Kansas Medical Center’s Transgenic and Gene Targeting Facility.
About Alex’s Lemonade Stand Foundation
Alex's Lemonade Stand Foundation (ALSF) emerged from the front yard lemonade stand of 4-year-old Alexandra “Alex” Scott, who was fighting cancer and wanted to raise money to find cures for all children with cancer. Her spirit and determination inspired others to support her cause, and when she passed away at the age of 8, she had raised $1 million. Since then, the Foundation bearing her name has evolved into a national fundraising movement and is one of the leading funders of pediatric cancer research in the U.S. and Canada. For more information, visit AlexsLemonade.org.