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Researchers decode biology of blood and iron disorders mapping out novel future therapies
Date:3/25/2013

erythropoiesis -- the process by which red blood cells (erythrocytes) are produced -- as a way to decipher and decode the two blood disorders beta-thalassemia and polycythemia vera.

Beta-thalassemia, a group of inherited blood disorders, is caused by a defect in the beta globin gene. This results in production of red blood cells that have too much iron, which can be toxic, resulting in the death of many of the blood cells. What are left are too few blood cells, which leads to anemia. At the same time, the excess iron from destroyed blood cells builds up in the body, leading to organ damage.

In polycythemia vera, a patient's bone marrow makes too many red blood cells due to a genetic mutation that doesn't shut down erythropoiesis -- the production of the cells.

The researchers studied both normal erythropoiesis, in which a person makes enough red blood cells to replace those that are old, and a mechanism called stress erythropoiesis, which flips on when a person requires extra blood cells -- such as loss of blood from an accident. The hormone erythropoietin (EPO) controls red blood cell production, and can also induce stress erythropoiesis. Iron is also essential, says Dr. Rivella. "The two well-known elements needed to switch between normal and stress erythropoiesis are EPO and iron," he says.

But Dr. Rivella and his team found that a third player is essential: macrophages, the immune cells that engulf cellular garbage and pathogens. Macrophages had been known to digest the iron left when old blood cells are targeted for destruction, but Dr. Rivella discovered that they also are necessary for stress erythropoiesis. He found macrophages need to physically touch erythroblasts, the factories that make red blood cells, in order for more factories to be created so that they can churn out red blood cells.

"No one knew macrophages were a part of emergency red blood cell production. We now know they provide fuel to push red blo
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Contact: Lauren Woods
Law2014@med.cornell.edu
646-317-7401
Weill Cornell Medical College
Source:Eurekalert

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