Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 5 4 2011 12 15 5 9 Majid Farshdousti Hagh Division of Laboratory Hematology and Blood Banking, Faculty of Medicine, Tabriz University of Medical Sciences, Tabrez, Iran Ali Dehghani Fard Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University,Tehran, Iran Najmaldin Saki Research Center of Thalassemia and Hemoglobinopathies, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Mohammad Shahjahani Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University,Tehran, Iran Saied Kaviani Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University,Tehran, Iran 2015 10 01 Hemoglobin F (HbF, α2γ2) 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, α2β2) 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. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/289 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/289/282