Chapter 7 Reactivation of Fetal Hemoglobin for Treating beta-Thalassemia and Sickle Cell Disease

摘要

Abstract Reactivation of fetal hemoglobin (HbF) in adult hematopoietic cells has the potential for great clinical benefit in patients bearing deleterious mutations in the beta-globin gene, such as p-thalassemia and sickle cell disease (SCD), since increasing the production of HbF can compensate for underproduction of beta-globin chains (in beta-thalassemia) and it can also disrupt sickle hemoglobin polymerization (in SCD). Thus for the past few decades, concerted efforts have been made to identify an effective way to induce the synthesis of HbF in adult erythroid cells for potential therapeutic relief from the effects of these beta-globinopathies. Chemical inducers of HbF as well as a number of transcription factors that are able to reactivate HbF synthesis in vitro and in vivo in adult erythroid cells have been identified. However, there has been only limited success in attempts to manipulate either the drugs or regulatory proteins, and in only a fraction of patients, and there is wide variation in individual response to these drugs or transcription factors. These studies highlight the importance for understanding the molecular mechanisms underlying hemoglobin switching so that future studies can be designed to treat these disorders.