Scientists at The Scripps Research Institute discovered enzyme that is responsible for keeping blood stem cells functional to prevent anaemia. Stem cells can generate any type of cell in the body, but to function properly they need time of inactivity. That is why this enzyme is so important – it is a key to maintaining healthy periods of inactivity, which may help to avoid cell damage and mutations.
Blood stem cells in question, also called hematopoietic stem cells, live in little niches in the bone marrow and are normally inactive, only dividing to self-renew about every two months. They become more active after severe bleeding or during infections, when mature blood cells are lost. When lost cells are replenished, stem cells have to become inactive again. This balance is crucially important and if it is disrupted it can lead to blood cancers, a loss of blood cells and an impaired ability to fight disease.
Diseases may strike both when stem cells are unable to regenerate or become hyperactive. Chronic myelogenous leukaemia is caused by such hyperactivity. Therefore, knowing that balance between active and inactive periods is very important, scientists set out to better the understanding about mechanisms that regulate activity of blood stem cells.
They focused on enzyme, known as ItpkB, because it was known that it controls a major signalling pathway in other cells that had been implicated in activating blood stem cells. Scientists hypothesized that ItpkB might dampen activating signalling in blood stem cells to keep them at rest. They started testing their hypothesis with mice that lacked the gene to produce ItpkB. Soon they found out that mice had hyperactive blood stem cells that soon stopped producing progenitor cells, which caused severe anaemia (decrease in the amount of red blood cells).
To explain how ItpkB works is a rather difficult task. But in short it can turn one inositol, called IP3, into an inositol called IP4. IP4 controls cell proliferation, cellular metabolism and aspects of the immune system. Without ItpkB blood stem cells skip the healthy periods of inactivity. Scientists then set out to find treatment to this condition.
ItpkB is an enzyme whose function can be controlled by small molecules, which makes it attractive for drug treatment. The researchers successfully treated animal models with an approved anti-cancer drug rapamycin. It halted the abnormal signalling process and prevented the excessive division of blood stem cells that lacked the enzyme. Now scientists will try to find out if the enzyme works the same in human bodies as well.
New findings now have to be translated into innovative therapies, targeting ItpkB to improve blood stem cell function in bone marrow failure syndromes. It could also help to increase the success rates of hematopoietic stem cells transplantation therapies for leukaemia and lymphomas. If new finding prove to be applicable for clinical use, innovative treatments will help people to cope with anaemia, blood cancer and immunodeficiency.