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Researchers show key protein necessary for normal development of red blood cells

Virginia Commonwealth University researchers studying hemoglobin genes, mutations of which play a role in genetic blood disorders like sickle cell anemia and beta-thalassemia, have shown in studies with mice that the KLF2 protein is crucial for making young red blood cells.

The findings may point researchers to future gene therapies for patients with sickle cell anemia and beta-thalassemia.

In the October issue of Blood, the journal of the American Association for Hematology, researchers demonstrated that a protein called KLF2 regulates the production of embryonic globin genes and the maturation and stability of embryonic red blood cells in a mouse model. Researchers observed that KLF2 is responsible for controlling and "turning on" the embryonic globin gene.

"Understanding how genes are turned on and off, and the switch from the embryonic globin gene to the adult beta-globin gene has clinical relevance to treatment of sickle cell anemia and beta-thalassemia," said Joyce A. Lloyd, Ph.D., associate professor of Human Genetics at VCU, and corresponding author for this study.

"Our findings are significant for future treatment of these blood disorders, potentially using gene therapies and other novel strategies," she said. In gene therapy, a normal DNA is inserted into cells to correct a genetic defect. To correct the defect or mutation, a gene may be replaced, altered or supplemented.

According to Lloyd, the production of blood cells involves a complex differentiation pathway that involves the interaction of many molecular players and proteins.

In humans, there are four globin genes clustered on chromosome 11 in the order in which they are "turned on" or expressed. These genes include the epsilon-globin gene, two gamma-globin genes and the beta-globin gene. Lloyd said that during fetal development, the embryonic epsilon-globin gene is active first, followed by the gamma-globin genes, and finally the adult form, beta-glo
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Source:Virginia Commonwealth University


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