This research project aims to investigate the link between preleukemic states including clonal hematopoiesis of indeterminate potential (CHIP) and monoclonal B-cell lymphocytosis (MBL) and the development of overt leukemia using data from the UK Biobank Pharma Proteomics Project (UKB-PPP). Preleukemic states are often detectable and serve as a risk factor for developing overt leukemia with a latency that can vary between months and decades. Despite existing risk scores to predict leukemic transformation from preleukemic states, their accuracy remains limited, often necessitating invasive and costly monitoring procedures. Thus, it is imperative to discover biological insights that can predict the progression of the disease. Protein-based biomarkers from blood offer a convenient and cost-effective avenue for testing and monitoring these biomarkers. By analyzing the proteomic data from a large cohort of individuals from the UKB-PPP, we aim to determine the prevalence and incidence of preleukemic states, understand its associations with demographic, clinical, and genetic factors, and identify proteomic signatures linked to preluekmia. Furthermore, we will investigate the molecular mechanisms driving the progression from perleukemia to leukemia by analyzing dynamic changes in protein expression patterns. Our final goal is to develop a predictive model for stratification of individuals with preleukemia based on their risk of developing leukemia, which may potentially lead to early detection and targeted interventions for improved patient outcomes. Overall, this research holds promise for advancing our understanding of leukemia development and improving strategies for its prevention and treatment. We plan to finish the project in 30 – 36 months with each specific aim divided and conquered separately.
