molecular mechanisms of hemoglobin f induction

hemoglobin f (hbf, α 2 γ 2 ) is a major contributor to the clinical heterogeneity and ameliorating agent observed in patients with the β-globin disorders including β-thalassemia and sickle cell disease (scd). during fetal life, hbf is the major hemoglobin but is largely substituted by adult hemoglobin (hba, α 2 β 2 ) following a globin expression switch after birth. increased γ-globin expression can reduce the clinical severity of β-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.