Chronic lymphocytic leukemia (CLL) patients with an unmutated (UM) immunoglobulin heavy chain variable region gene (IGHV) typically have poorer prognosis and require earlier treatment compared to those with mutated IGHV. Nevertheless, disease progression among UM-CLL patients is heterogeneous, with some experiencing stable disease and prolonged time to first treatment (TTFT). Because the cellular proteome directly reflects cell function, comprehensive proteomic and phosphoproteomic profiling may improve prediction of progression of UM-CLL and uncover novel biomarkers