PROJECT SUMMARY

VEXAS is a recently discovered disease where a genetic mutation acquired in the blood causes severe inflammation throughout the body. About half of patients with VEXAS are diagnosed with MDS. Our preliminary work has identified mutations that cause VEXAS but are missed by standard clinical assays. In this study, we propose to identify and characterize novel VEXAS-causing mutations and predict which VEXAS patients respond to azacytidine, a drug commonly used for MDS. First, we will screen patients with VEXAS-like symptoms for potentially missed mutations and understand how they disrupt the gene. Second, we will compare patients with different mutation types to see if they have different symptoms, blood problems, or chances of developing MDS. Third, we will study why some patients respond to azacitidine, a drug used to treat both MDS and VEXAS, while others do not. By comparing patients before and after treatment, we hope to find markers that predict who will benefit and identify other treatment strategies. VEXAS-MDS patients desperately need better treatments. Our goals are to diagnose patients currently being missed, understand why some develop more severe disease, including MDS, and predict who will respond to treatment. Overall our study aims to improve outcomes and quality of life for patients with inflammation and MDS.