Hemoglobin switching and modulation: genes, cells, and signals

Abstract

A detailed understanding of hemoglobin production in erythroid cells is of fundamental clinical importance for the treatment of hemoglobinopathies. Several hundred scientific reports and dozens of reviews describe this intriguing topic of research. Early studies demonstrated the temporal nature of a hemoglobin-switching phenomenon during development in the circulating erythrocytes of humans. The focus then shifted from descriptive to experimental analyses and model systems in an effort to define the switching mechanisms. The application of molecular biology in those experimental models has been a primary focus for the last two decades. Today, advances in the fields of stem cell biology and signal transduction are being integrated with those genetic studies. Genomic and proteomic approaches are also being developed to provide a more robust description of the biologic variables involved. This review highlights recent advances in erythroid genetics and cellular biology with an emphasis upon the modulation of fetal hemoglobin expression during the maturation of adult human erythrocytes.