Abstract

Each day humans produce more than 200 billion mature blood cells from 50,000-200,00 hematopoietic stem cells (HSCs). Like all somatic cells these long-lived HSCs inexorably acquire somatic mutations over time. Most mutations have no conspicuous consequences, but a small minority impart their host HSC with a fitness advantage and drive it to expand clonally. This phenomenon, known as clonal haematopoiesis (CH), becomes ubiquitous with advancing age and is associated with an increased risk of blood cancers, as well as several non-haematological diseases. Over the last few years, we have been working to decipher the causes and consequences of CH, with a particular focus on i) understanding the basis of clonal expansion, ii) quantifying the risk of progression to blood cancer and iii) developing approaches to prevent such progression. In my talk, I will describe our progress with the hope of convincing you that we can make blood cancer prevention a clinical reality in our lifetime.