Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 7 3 2013 09 15 41 46 Fakher Rahim Toxicology Research Center, Ahvaz University of Medical Sciences, Ahvaz, Iran. Hossein Allahmoradi General Practitioner, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Fatemeh Salari Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Mohammad Shahjahani Department of Hematology and Blood Banking, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Ali Dehghani Fard Sarem Cell Research Center- SCRC, Sarem Women's Hospital, Tehran, Iran. Seyed Ahmad Hosseini Department of nutrition, Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Hadi Mousakhani Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 2015 10 14 Potent induction of fetal hemoglobin (HbF) production results in alleviating the complications of β-thalassemia and sickle cell disease (SCD). HbF inducer agents can trigger several molecular signaling pathways critical for erythropoiesis. Janus kinase/Signal transducer and activator of transcription (JAK/STAT), mitogen activated protein kinas (MAPK) and Phosphoinositide 3-kinase (PI3K) are considered as main signaling pathways, which may play a significant role in HbF induction. All these signaling pathways are triggered by erythropoietin (EPO) as the main growth factor inducing erythroid differentiation, when it binds to its cell surface receptor, erythropoietin receptor (EPO-R) HbF inducer agents have been shown to upregulate HbF production level by triggering certain signaling pathways. As a result, understanding the pivotal signaling pathways influencing HbF induction leads to effective upregulation of HbF. In this mini review article, we try to consider the correlation between HbF inducer agents and their molecular mechanisms of γ-globin upregulation. Several studies suggest that activating P38 MAPK, RAS and STAT5 signaling pathways result in efficient HbF induction. Nevertheless, the role of other erythroid signaling pathways in HbF induction seems to be indispensible and should be emphasized. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/445 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/445/352