Petter Woll

Errors in the genetic code in DNA occur every time a cell divides. A hematopoietic stem cell can thus accumulate more than 1000 DNA mutations during a person's lifetime. Some mutations occur in genes that cause altered cell properties and an increased risk of leukemia. In many healthy elderly individuals over 70, blood cells with mutations linked to leukemia have been detected. This gives a tenfold increased risk of developing leukemia, but it is not known how these mutations increase the risk. As we currently cannot predict which healthy individuals with mutations will develop leukemia, there is no clinical treatment for these. We focus on studying cells with DNA changes that give an increased risk of leukemia, isolated from healthy elderly people or healthy mice, before they develop leukemia. In this way, we can follow how these cells behave during normal blood formation and in situations where there is an increased need for new blood cells, for example during inflammation or chemotherapy treatment. This may provide new insights into which genetic and cellular mechanisms change normal blood cells into leukemia cells. Through these studies, we can identify which mutations, in combination with altered blood formation, give rise to leukemia. This research aims to identify genetic and cellular factors that influence the development of leukemia in aging. The result can be used to find at an earlier stage the individuals who are at high risk of developing leukemia and clinically treat them to prevent them from developing leukemia. Finally, these studies can reveal important biological properties of the cells that are destined to become leukemia cells, which can be used for targeted therapies.