Biennial Report of the Director

Research in Diseases, Disorders, and Health Conditions
Chronic Diseases and Organ Systems
Blood Diseases

Chronic anemias result from a deficiency of red blood cells or an abnormality in hemoglobin production, as is the case with sickle cell diseases and Cooley’s anemia. Patients can experience pain, fatigue, and other serious health problems. Chronic inherited bleeding disorders, such as hemophilia and von Willebrand disease, leave patients at risk for uncontrollable bleeding.
NIH supports research on the causes, prevention, and treatment of nonmalignant blood diseases, including anemias, sickle cell disease, and thalassemia; premalignant processes such as myelodysplasia and myeloproliferative disorders; hemophilia and other abnormalities of hemostasis and thrombosis; and immune dysfunction. Efforts led by NIDDK include:

A commontreatment for severe anemia is blood transfusion. However, multiple transfusions can lead to iron overload which can be toxic to certain organs, in particular the liver and heart. While there are drugs to reduce iron levels, additional strategies to treat anemia and limit iron overload are needed. When mice with β-thalassemia were genetically altered to make more hepcidin than usual, they exhibited not only reduced organ iron overload, but also a remarkable improvement of their anemia. These findings led the scientists to suggest that the development of therapeutic interventions that could increase hepcidin levels or act similarly to hepcidin might help reduce excess iron absorption in individuals with β-thalassemia.250
Fetal hemoglobin is replaced by adult hemoglobin within the first year after birth. Reactivation of fetal hemoglobin can treat red blood cell diseases like sickle-cell anemia. Scientists recently reported that a small deletion in a region of chromosome 6 may be the most significant functional variant accounting for different levels of fetal hemoglobin (HbF) in people of Chinese, European, or African American ancestry. A DNA fragment surrounding this deletion site was shown to regulate expression of the gene for gamma globin—a component of HbF—when tested in vitro. In particular, gamma-globin gene activation was found to be stronger when this short stretch of DNA was deleted than when it was present.251
Priority research areas identified by NIH include the Stimulating Hematology Investigation: New Endeavors (SHINE) program, which is intended to promote innovative, high quality hematology research relevant to the mission of the NIDDK. In the SHINE program, NIDDK invites investigator-initiated research project grant applications in specific areas of basic and translational hematology research where needs and opportunities for progress are particularly timely. Specific research topic areas supported by the SHINE program include: ribosomes and their role in disease; non-erythroid expression and function of erythropoietin receptors; heme regulation during erythropoiesis; anemia of inflammation and of chronic disease; iron overload; and biology and pathophysiology of myelodysplastic syndrome.

250 Gardenghi S, et al. J Clin Invest. 2010;120:4466–77. PMID: 21099112.
251 Farrell JJ, et al. Blood. 2011;117:4935–45. PMID: 21385855.