PROJECT SUMMARY

Myelodysplastic syndromes (MDS) are blood disorders in which the bone marrow does not produce healthy blood cells and can progress to leukemia. Some patients develop MDS after years of chronic inflammation, but why this happens is not well understood. This project focuses on VEXAS syndrome, a recently discovered inflammatory disease caused by mutations in blood stem cells. While many VEXAS patients have severe inflammation, only some go on to develop MDS. This provides a unique opportunity to understand how long-term inflammation can push blood stem cells toward cancer. In this study, we will compare blood stem cells from VEXAS patients who developed MDS with those who did not. Using advanced single-cell technologies, we will examine how these cells respond to stress, how they turn genes on and off, and how they process genetic messages. Our goal is to identify early changes that make some cells more likely to become cancerous. By uncovering how inflammation and cellular stress drive MDS development, this work will improve our understanding of MDS biology, help identify patients at higher risk, and reveal new targets for treatment. Ultimately, these insights may guide more precise and earlier interventions for patients with MDS and related blood disorders.