GATA2-GATA1 Axis in Diamond Blackfan Anemia
Abstract
Diamond Blackfan Anemia (DBA) is a serious hereditary disease characterized by severe anemia caused by failure to produce enough red blood cells. The disease is diagnosed in young children who become dependent on frequent blood transfusions for many years, occasionally for a lifetime. Currently there is no efficient therapy. Based on a recent mouse model that we created, we suggest that the anemia may be, at least partially, caused by imbalance between two proteins, GATA1 and GATA2, that regulate blood development. GATA1 regulates the development of red blood cells. For this purpose, GATA1 blocks the production of GATA2. We found that when GATA1 is mutated, as was recently discovered in some children with DBA, GATA2 remains elevated. We hypothesize that the persistent GATA2 blocks the production of mature red blood cells and causes anemia. To examine this hypothesis, we will create a mouse model in which there is half the amount of GATA2. We will test if the reduction of GATA2 can rescue the anemia caused by the abnormally mutated GATA1. We will apply sophisticated genomic technologies to identify how GATA2 works so that we might discover specific genes and proteins that could be therapeutically targeted to alleviate the anemia. While only few patients with DBA have mutations in GATA1, recent research has demonstrated that many, maybe most, patients with DBA have low levels of the GATA1 protein, which may explain their anemia. If our GATA2/GATA1 hypothesis proves correct, targeting the genes and proteins regulated by excess of GATA2 may correct the anemia and prevent the dependency on blood transfusions of many patients with DBA.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510227
Entities
People
- Shai Izraeli
Organizations
- Sheba Medical Center
- United States Army