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New approach to sickle-cell disease shows promise in mice
Date:12/7/2009

he globin produced was of this fetal type. In adult mice (8-10 weeks old), inactivation of the BCL11A gene in the blood system resulted in more than a 1,000-fold increase in gamma-globin production in bone marrow erythroblasts (the precursors to red blood cells) as compared with control mice. This increase was rapid and persisted during the course of the experiments (up until the mice were 25 weeks old).

This line of research began with comprehensive gene association studies, published in 2008 with collaborators at the Broad Institute of Harvard and MIT (http://www.childrenshospital.org/newsroom/Site1339/mainpageS1339P1sublevel452.html). These studies, involving 1600 patients with sickle cell disease, identified five DNA sequence variants (altered strings of genetic code) that correlated with fetal hemoglobin levels. BCL11A, on chromosome 2, had the largest effect, and Orkin and Vijay Sankaran, an MD-PhD student working with Orkin, later demonstrated that this gene directly suppresses fetal hemoglobin production.

If these preliminary results in mice hold up in human studies, inactivating BCL11A may also help patients with thalassemia, another blood disorder involving abnormal hemoglobin, adds Orkin.


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Contact: Rob Graham
rob.graham@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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