Author/Authors :
Rahim، Fakher نويسنده Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , , Allahmoradi، Hossein نويسنده General Practitioner, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Allahmoradi, Hossein , Salari، Fatemeh نويسنده Department of Law, Kerman Science and Research Branch, Islamic Azad University, Kerman, Iran , , Shahjahani، Mohammad نويسنده Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran , , Fard، Ali Dehghani نويسنده Sarem Cell Research Center- SCRC, Sarem Womens Hospital, Tehran, Iran. Fard, Ali Dehghani , Hosseini ، Seyed Ahmad نويسنده , , Mousakhani، Hadi نويسنده Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Mousakhani, Hadi
Abstract :
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.
