Molecular Studies for the Early Detection of Philadelphia-Negative Myeloproliferative Neoplasms

V617F is the predominant driver mutation in patients with Philadelphia-negative myeloproliferative neoplasms (MPN). mutations are also frequent in clonal hematopoiesis of indeterminate potential (CHIP) in otherwise "healthy" individuals. However, the period between mutation acquisition and MPN diagnosis (known as latency) varies widely between individuals, with mutations detectable several decades before diagnosis and even from birth in some individuals. Here, we will review the current evidence on the biological factors, such as additional mutations and chronic inflammation, which influence clonal expansion and may determine why some -mutated individuals will progress to an overt neoplasm during their lifetime while others will not. We will also introduce several germline variants that predispose individuals to CHIP (as well as MPN) identified from genome-wide association studies. Finally, we will explore possible mutation screening or interventions that could help to minimize MPN-associated cardiovascular complications or even delay malignant progression.