Myelodysplastic syndrome (MDS) in children is a rare group of disorders in which blood-making stem cells stem cells: Cells in the body that develop into other cells. There are two main sources of stem cells. Embryonic stem cells come from human embryos and are used in medical research. Adult stem cells in the body repair and maintain the organ or tissue in which they are found. Blood-forming (hemapoietic) stem… in the bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. (BM) fail to work properly. As a result, patients develop low blood counts and have increased risk to develop leukemia with cancerous cells, referred to as blasts blasts: See Blast Cells. , also called refractory refractory: Not responsive to treatment or cure. For example, refractory anemia is a low red blood cell count that doesn't respond to standard treatments. cytopenia cytopenia: (sie-tuh-PEE-nee-uh) A shortage of one or more blood cell types. Also called a low blood count. of childhood (RCC). Although RCC is the most common category, we do not fully understand its molecular basis (gene and chromosome changes associated with the disease). Some patients with RCC have empty BM which might be mistaken for aplastic anemia aplastic anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… , while others have acquired changes that predispose them to more advanced MDS and leukemia. Therefore, it is often difficult to tell apart RCC from other blood disorders such as inherited marrow failure or acquired aplastic anemia. There is an urgent need study the genetics to find specific genetic changes that can be inherited or acquired. In this proposed study, we will use new genomic technologies in children with MDS. In Aim 1 of our study, we will focus on discovering acquired genetic changes in RCC by using sequencing methods with very high detection rates. We anticipate to find new mutations that will help better diagnose the patients, allowing for more tailored therapy. In Aim 2, we will sequence thousands of single bone barrow cells or children with MDS. We expect that with this approach we will answer which genetic changes come first in the process of clonal evolution, and which contribute to the development of a more aggressive disease resulting in leukemia. Altogether, we aim to better understand MDS in children and, most importantly, use our findings to improve patient care and long-term outcomes.