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Rahim F, Allahmoradi H, Salari F, et al. Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs. Int J Hematol Oncol Stem Cell Res. 2013;7(3):41-6
Rahim, F., Allahmoradi, H., Salari, F., Shahjahani, M., Fard, A. D., Hosseini, S. A., & Mousakhani, H. (2013). Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs. International journal of hematology-oncology and stem cell research, 7(3), 41-6.
Rahim, Fakher, et al. "Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs." International journal of hematology-oncology and stem cell research vol. 7,3 (2013): 41-6.
Rahim F, Allahmoradi H, Salari F, Shahjahani M, Fard AD, Hosseini SA, Mousakhani H. Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs. Int J Hematol Oncol Stem Cell Res. 2013;7(3):41-6. PMID: 24505534; PMCID: PMC3913148.
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Int J Hematol Oncol Stem Cell Res. 2013;7(3):41-6.

Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.

International journal of hematology-oncology and stem cell research

Fakher Rahim, Hossein Allahmoradi, Fatemeh Salari, Mohammad Shahjahani, Ali Dehghani Fard, Seyed Ahmad Hosseini, Hadi Mousakhani

Affiliations

  1. Toxicology Research Center, Ahvaz University of Medical Sciences, Ahvaz, Iran.
  2. General Practitioner, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  3. Research Center of Thalassemia & Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  4. Department of Hematology and Blood Banking, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
  5. Sarem Cell Research Center- SCRC, Sarem Women's Hospital, Tehran, Iran.
  6. Department of nutrition, Allied Health Sciences School, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

PMID: 24505534 PMCID: PMC3913148

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.

Keywords: Fetal hemoglobin; Sickle cell disease; β-thalassemia

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