Modeling Juvenile Myelomonocytic Leukemia with Patient-Derived Induced Pluripotent Stem Cells

Project Goal
This application leverages the complementary skills of three physician-scientists with expertise in blood development, stem cell biology and pediatric oncology to study juvenile myelomonocytic leukemia (JMML), a rare and frequently fatal cancer affecting young children. Laboratory studies of JMML, including the development of new treatments, are hindered by limited availability of tissue samples from young patients and the inability to expand malignant cells in the tissue culture dish.

To relieve this bottleneck, we are adapting innovative technologies in stem cell biology for the study of JMML. Specifically, we created induced pluripotent stem cells (iPSCs) from JMML patients. These iPSCs can be expanded extensively in culture and manipulated further to generate large quantities of blood cells that closely resemble the malignant bone marrow cells of JMML. We will use these cells for preclinical studies to identify new drugs with efficacy against JMML and to study newly identified genes that may influence treatment responses and survival of patients. Our studies promise to better elucidate the biology of JMML and identify more effective therapies. More generally, we hope to establish new experimental paradigms in which tumor-derived iPSCs can be used to study many types of pediatric cancer.