The intrinsic genetic and epigenetic regulator factors as therapeutic targets, and the effect on fetal globin gene expression

ABSTRACT

Introduction: The effort to induce fetal globin or Hb F gene expression as an alternative therapy for blood transfusion has been ongoing for few decades, with promising results evident in patients with hemoglobinopathies. Although the clinical outcomes have been satisfactory and significant, there are still concerns about the safety of Hb F inducers in the long-term. There are potent inducers which lose their potency and safety over the course of therapy.

Area covered: In this work, efforts have been made to review the latest findings on intrinsic genetic and epigenetic factors which are able to induce the gene expression of fetal globin in adult patients with beta (β)-thalassemia Major, Intermedia and sickle cell disease (SCD).

Expert commentary: To meet a satisfying therapeutic outcome in patients with hemoglobinopathies, in addition to adopting a potent Hb F inducer, a continuous level of gamma (γ)-globin gene over the course of therapy in safety condition also needs to be considered. Therefore, to reach this aim, it is suggested that the experiment designers consider the safety and long-term characteristics of the inducers simultaneously, by examining their synergistic effects.

KEYWORDS:

• Beta (β)-thalassemia
• epigenetic Hb F regulators
• gamma (γ)-globin
• genetic Hb F regulators
• long-term induction

Acknowledgments

The study space allocated by Bioinformatics Department of Pasteur Institute of Iran during the study on this project is highly appreciated, with special thanks to Dr. M. Mafakheri for her warm welcoming.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The manuscript has not been funded.