Hematopoietic stem cell function in familial platelet disorder therapy
Genetic studies have identified a number of genes that when mutated predispose individuals to blood cancers. In addition, these mutations can promote other health complications throughout their lifetime. For example, children that inherit a mutation in the gene RUNX1 have Familial Platelet Disorder, they live with bleeding problems and, in many cases, autoimmune complications. In addition, affected children have a high incidence of blood cancer during their childhood or later in life. Currently, there are not effective therapies to prevent the development of blood cancer. Patients that develop blood cancers with a RUNX1 mutation are treated with chemotherapy and allogeneic stem cell transplantation.
Important advances in genome editing technologies provide an opportunity to correct mutations in blood stem cells with high efficiency.
The goal of this project is to determine if the correction of the RUNX1 mutation in blood stem cells can restore their normal function and prevent cancer, using a mouse model for Familial Platelet Disorder. These studies may guide future efforts to develop autologous stem cell transplantation protocols that efficiently correct the RUNX1 mutation in the blood stem cells for transplant back into the patient as a curative therapy. The outcome of this study may also serve for the application of similar approaches to other inherited blood cancers.