PROJECT SUMMARY

Myelodysplastic syndromes (MDS) are a group of age-related marrow failure disorders characterized by cytopenia and anemia. This is caused by the functional decline of hematopoietic stem cells in the marrow because of acquired genetic mutations that corrupt their ability to make blood cells effectively. Clinical management of MDS remains challenging with limited treatments available, and stem cell transplantation remains the only curative therapy. However, most patients are unable to receive transplantation due to advanced age and co-morbidities. Thus, there is a pressing need to better understand the complexity of the disease which can lead to the development of novel therapies. In this proposal, we plan to understand how certain age-related factors favor the growth of MDS cells and how they corrupt their neighboring cells in the bone marrow. We plan to systematically analyze the cellular and molecular changes in MDS cells and chart their interactions with components of the bone marrow microenvironment using disease-relevant models and molecular profiling approaches. We anticipate that the successful completion of this proposal will lead to the discovery and development of new treatment options that will hopefully improve the outcomes of MDS patients.