Biomarkers in clonal haematopoiesis of indeterminate potential (CHIP) linking cardiovascular diseases, myeloid neoplasms and inflammation

Abstract

There is increasing evidence that points to ubiquity of clonal haematopoiesis of indeterminate potential (CHIP) especially with rising age. CHIP has been associated with a multitude of inflammatory, cardiovascular and malignant conditions. In this review article, we evaluate the current literature on CHIP and clinical associations with cardiovascular and haematological diseases. We also discuss high risk features of CHIP that predispose to haematological malignancies, as well as further zoom in on the association between clonal haematopoiesis and therapy-related myeloid neoplasm (tMN). CHIP increases risk of atherosclerotic cardiovascular disease and other cardiovascular conditions such as heart failure, arrhythmias and valvular disease. Hematopoietic clones with mutations in TP53 and spliceosome gene U2AF1 in particularly have repeatedly been shown to increase risk for AML. Other factors such as increased clonal size i.e. variant allele fraction (VAF), clonal complexity have also been shown to increase risk for haematological malignancy. In this comprehensive review, we consolidate the most recent advancements in the understanding of clonal haematopoiesis of indeterminate potential (CHIP) and its associations with cardiovascular and haematological disease. This review is also one of the first to focus on potential biochemical markers routinely utilized in clinical practice that may suggest a more sinister progression of CHIP. We hope to provide physicians with a nuanced perspective on the evolving landscape of CHIP, and offering valuable insights into its clinical implications and potential prognostic indicators.