PROJECT SUMMARY

Myelodysplastic syndromes (MDS) in children are rare disorders of the blood stem cell. Most of the patients have inherited mutations which predispose them to MDS development; some patients have overactive immune system and inflammation that contributes to MDS development. Acquired (somatic) genetic changes can develop in the bone marrow over time. These can drive the disease process towards leukemia, but some can also undergo “natural gene therapy” and rescue the abnormal stem cell. Current methods often miss these changes especially in the beginning when they are found only in a few blood cells. Furthermore, we do not know in which type of stem cells these events occur. This knowledge is important because some patients might require early bone marrow transplantation as a therapy (if a “bad” genetic change is found), while other patients might have rescued their bone marrow (“good” genetic change) and do not require any further therapy. In this project we will use new single cell genetic assays and cell biology methods to understand the complexity and clinical importance of these genetic changes in children with MDS. The results will hopefully contribute to better understanding why some patients develop leukemia, while others undergo natural gene therapy.