Fig. 3.

A, Haematopoietic stem cells (HSCs) reside in the bone marrow. They have proliferative and self-renewing properties (arrow). These HSCs give rise to all our differentiated blood cells, including those of the immune system (listed). During our lifetime, mutations arise (cell with cross), but most have no consequences, although rare oncogenic mutations can lead to blood cancers. Their offspring make up a small percentage of total blood cells. B, As we age, we accumulate mutations in our HSCs. These may be due to somatic mutations; epigenetic changes from environmental factors, including diet; and inflammation from chronic diseases, such as cardiovascular disease (CVD) and periodontal disease. Most, again, are inconsequential. However, a mutation that leads to a selective advantage of an HSC may arise (cells with X). This advantage may be increased renewal capacity or increased proliferative capacity. As a result, there is a skewing in the differentiated cell population such that they carry that mutation, and as we age, this becomes more pronounced. Less than 1% per year may result in a blood cancer. More commonly, however, this clonal expansion of differentiated cells carrying the mutation is associated with a 40% increase in risk of CVD.