Abstract
PURPOSE OF REVIEW: Small amounts of fetal hemoglobin can be expressed in a subset of adult red blood cells called F-cells. This review examines the potential mechanisms and clinical implications of the heterogeneity of fetal hemoglobin expression. RECENT FINDINGS: Although the heterocellular nature of fetal hemoglobin expression in adult red blood cells has been noted for over 70 years, the molecular basis of this phenomenon has been unclear. Recent discoveries of novel regulators of fetal hemoglobin as well as technological advances have shed new light on these cells. SUMMARY: Fetal hemoglobin reactivation in adult red blood cells through genetic or pharmacological approaches can involve both increasing the number of F-cells and cellular fetal hemoglobin content. New technologies enable the study and eventually the improvement of these parameters in patients with sickle cell disease and β-thalassemia.