TSRI team discovers enzyme that keeps blood stem cells functional to prevent anemia

IMAGE:Karsten Sauer, Ph.D., is an associate professor at The Scripps Research Institute. view more

Credit: Photo courtesy of The Scripps Research Institute.

LA JOLLA, CA - March 23, 2015 - Stem cells can generate any type of cell in the body, but they are inactive most of the time--and for good reason. When stem cells become too active and divide too often, they risk acquiring cell damage and mutations. In the case of blood stem cells (also called hematopoietic stem cells or HSCs), this can lead to blood cancers, a loss of blood cells and an impaired ability to fight disease.

Now scientists at The Scripps Research Institute (TSRI) have found that a particular enzyme in HSCs is key to maintaining healthy periods of inactivity. Their findings, published recently in the journal Blood, show that animal models without this enzyme experience dangerous HSC activation and ultimately succumb to lethal anemia.

"These HSCs remain active too long and then disappear," said TSRI Associate Professor Karsten Sauer, senior author of the new study. "As a consequence, the mice lose their red blood cells and die."

With this new understanding of the enzyme, called Inositol trisphosphate 3-kinase B (ItpkB), scientists are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, lymphoma and immunodeficiencies.

Stem Cells Need Rest

HSCs are a type of adult stem cell that lives in little niches in the bone marrow. They are normally inactive, or "quiescent," and only divide to self-renew about every two months.

However, when mature blood cells are lost, for example through severe bleeding or during infections, HSCs become activated to generate new "progenitor" cells--the cells that replenish the blood supply and produce immune cells to fight disease. Once the blood cells have been replenished, the HSC become quiescent again.

The balance between inactivity and activity is important because HSC activation generates side products that harm HSC. In addition, every division introduces a risk of mutation, sometimes leading to cancer. "It's like a car wearing down its own engine while it is doing its work," said Sauer. "Like people, HSCs need long periods of rest to remain healthy and work well."

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TSRI team discovers enzyme that keeps blood stem cells functional to prevent anemia