Project 466783

Monoclonal B-cell lymphocytosis (MBL) is a pre-condition of chronic lymphocytic leukemia (CLL), which is associated with weakened immunity and greater vulnerability to infections and cancer development. It remains unknown why some individuals with MBL progress to CLL while others do not. Older biological age and changes in DNA methylation (DNAm), one of the biological processes that control gene expression, may be involved. Here, we will measure the methylation levels of DNA isolated from people with MBL who progress to CLL (progressors) compared with those who do not (non-progressors). We will use established tools to determine the epigenetic ages of both groups and statistical modeling to identify the differences in DNAm between the two groups and use those to predict progression. We expect that progressors will be epigenetically older than non-progressors, and we also expect to find the DNAm sites that are crucial in predicting MBL progression. The results of this project will further our understanding of epigenetic contributions to the progression of MBL to CLL. The results may also provide the rationale for exploring new treatments that target abnormal DNA methylation in early-stage CLL patients.