Fetal hemoglobin chemical inducers for treatment of hemoglobinopathies.
The switch from fetal ((G)gamma and (A)gamma) to adult (beta and delta) globin gene expression occurs at birth, leading to the gradual replacement of HbF with HbA. Genetic regulation of this switch has been studied for decades, and the molecular mechanisms underlying this developmental change in gene expression have been in part elucidated. The understanding of the developmental regulation of gamma-globin gene expression was paralleled by the identification of a series of chemical compounds able to reactivate HbF synthesis in vitro and in vivo in adult erythroid cells. Reactivation of HbF expression is an important therapeutic option in patients with hemoglobin disorders, such as sickle cell anemia and beta-thalassemia. These HbF inducers can be grouped in several classes based on their chemical structures and mechanisms of action. Clinical studies with some of these agents have shown that they were effective, in a part of patients, in ameliorating the clinical condition. The increase in HbF in response to these drugs varies among patients with beta-thalassemia and sickle cell disease due to individual genetic determinants.
Testa
Ugo
U
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. ugo.testa@iss.it
D000818:Animals; D002986:Clinical Trials as Topic; D005319:Fetal Hemoglobin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006453:Hemoglobinopathies / Q000097:blood* / Q000188:drug therapy*; D006801:Humans
D005319:Fetal Hemoglobin