The bone marrow of a healthy adult produces more than 100.000.000.000 new blood cells every day to replace those lost by wear and tear. Half of these become red blood corpuscles responsible for transporting oxygen around the body, while the others are white cells with a range of immune functions. Because the most common white cells have a life span of just hours to days, while the red corpuscles remain in the bloodstream for around 3 months, normal blood has around 1000x more red than white cells.
This changes in leukemia (Greek “white blood”), in which a disturbance in the balance of cell production in the marrow leads to an abnormal accumulation of white cells. In order to devise new and better treatments, we need to understand how normal blood cell production (hematopoiesis) is controlled and how these controls become overridden in leukemia and related diseases.
More than half a century of research in this area has revealed the ground plan of hematopoiesis, with a single type of multi-potential hematopoietic stem cell giving rise to 8 major blood cell types. The stem cells themselves spend most of their time in a secluded niche in the bone marrow, dividing only rarely to produce daughter cells that move out of the niche and undergo multiple rounds of division. As these cell divide, they gradually take on the characteristics of a particular cell type in a process termed differentiation.
Cell division and differentiation are influenced by signals in the form of growth factors and hormones delivered by the blood stream or by local bone marrow “stromal” cells. Each signal is recognized by a specific receptor on or in the hematopoietic cell. Binding of the signal to the receptor triggers a response known as signal transduction that can affect survival, migration, proliferation and differentiation by changing the pattern of gene expression. Mutations in the genes involved disrupt the normal control and can lead to diseases such as leukemia.
