Molecular mechanisms of hemoglobin F induction

Abstract

Hemoglobin F (HbF, ? 2? 2) is a major contributor to the clinical heterogeneity and ameliorating agent observed in patients with the ?-globin disorders including ?-thalassemia and sickle cell disease (SCD). During fetal life, HbF is the major hemoglobin but is largely substituted by adult hemoglobin (HbA, ? 2? 2) following a globin expression switch after birth. Increased ?-globin expression can reduce the clinical severity of ?-thalassemia and SCD. Therefore, increase in HbF production has served as a longstanding goal. The progression of target-based therapeutics has been confused by limited comprehension of molecular mechanisms of gamma-globin gene expression. However, recent discoveries of regulators of HbF level represent a major development and provide new opportunities in employing novel rational therapeutic strategies. In this review, molecular mechanisms of hemoglobin F induction will be discussed.