Genetic Discovery Could Circumvent Splenectomy for Cooley's Anemia Sufferers

New research may have discovered the precise role of a gene responsible for the mutated red blood cells (RBCs) in one of the world's most common blood disorders, beta-thalassemia (commonly known as Cooley's Anemia), which could prevent a splenectomy.

Researchers from the Weill Cornell Medical College (WCMC, New York, NY, USA) observed that in the thalassemic mice, a greater than normal percentage of erythroid cells were in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, Ki-67, and the anti-apoptotic protein Bcl-XL. They also differentiated less that normal erythroid ones in vitro. In order to investigate whether Janus kinase 2 (JAK2, a protein tyrosine kinase) could be responsible for the limited cell differentiation, the researchers administered a Jak2 inhibitor, numbered TG101209, to normal and thalassemic mice. The researchers found that exposure to TG101209 dramatically decreased the spleen size but also affected anemia. The study was published in the May14, 2008, online issue of the journal Blood.

"While our data do not exclude a role for apoptosis in erythropoiesis, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates erythropoiesis in thalassemia,” concluded senior author Stefano Rivella, Ph.D., an assistant professor of genetic medicine in pediatrics at WCMC. "In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.”

In Cooley's anemia, hemoglobin is mutated and non-functioning, resulting in a low RBC count. Common symptoms of the disease include fatigue, shortness of breath, and an enlarged spleen, called splenomegaly, caused by a buildup of malformed RBCs within the body. The spleen works to filter out these unhealthy cells in order to protect the body from harm, such as in a stroke, but eventually the spleen becomes over-stuffed and is commonly surgically removed (splenectomy) in order to prevent a potentially fatal burst. Unfortunately, after the spleen is removed, patients are at a much greater risk for stroke and infections. Along with sickle-cell anemia, Cooley's anemia is the most commonly inherited disease in the world, affecting many people of Mediterranean descent. The World Health Organization (WHO) has estimated that between 50,000-100,000 children are born with the disease every year.


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