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Enzyme Essential to Red Blood Cell Production and Regulation Isolated

Enzyme Essential to Red Blood Cell Production and Regulation Isolated

A new study by researchers at St. Jude Children’s Research Hospital, published in the May 1st issue of Cell, has identified an enzyme crucial to the production of red blood cells and platelets.

Scientists have known for years that cytokines are necessary for the production and regulation of blood cells. Little is known, however, about how these cytokines work within the body to perform a function as essential and basic as blood cell production.

Researchers at St. Jude Hospital have now shown that an enzyme called Jak2 must be present so that the cyto-kine, erythropoietin, can function properly. Without the presence of Jak2, the cells that should respond to erythropoietin fail to do so.

"Our study shows that the Jak2 kinase is essential for erythropoietin to trigger the production of red blood cells," said James Ihle, PhD, chairman of the biochemistry department, St. Jude Children’s Research Hospital. "If Jak2 is not present, or not working properly, red blood cells cannot be produced, or they are produced incorrectly, as in the case of leukemia and anemia."

According to Dr. Ihle, a greater understanding of Jak2 and red blood cell production will help physicians and scientists develop therapies that can target malfunctioning cells and activate or deactivate the ability of these cells to respond to cytokines as necessary.

Jak2-Deficient Mice Compared to Healthy Mice

Dr. Ihle and a team of researchers zeroed in on the effects of Jak2 by comparing mice that lacked the Jak2 protein to healthy mice. As embryos, mice lacking Jak2 failed to respond to erythropoietin and did not produce red blood cells--proof that Jak2 is essential for processing erythropoietin. Studies of the mutant mice also demonstrated that Jak2 is needed for the proper functioning of thrombopoietin and for the production of platelets. Other cytokines, such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, and interferon-gamma, were also found to require Jak2 for their responses in cells.

 "Through this type of genetic research and therapy, we will be able to better determine why children have blood disorders. That information can help us develop new and better treatments that address specific malformations within the body’s genetic code," added Dr. Ihle.

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