Fetal hemoglobin regulation in β-thalassemia: heterogeneity, modifiers and therapeutic approaches

ABSTRACT

Introduction: Stress erythropoiesis induces fetal hemoglobin (HbF) expression in β-thalassemias, however the level of expression is highly variable. The last decade has seen dramatic advances in our understanding of the molecular regulators of HbF production and the genetic factors associated with HbF levels, leading to the promise of new methods of the clinical induction of HbF.

Areas covered: This article will review the heterogeneity and genetic modifiers of HbF and HbF induction therapy in β-thalassemia.

Expert commentary: One promising curative β-thalassemia therapy is to induce HbF synthesis in β-thalassemic erythrocytes to therapeutic levels before clinical symptom occurs. Further understanding of HbF level variation and regulation is needed in order to predict the response from HbF-inducing approaches.

KEYWORDS:

• Fetal hemoglobin
• HbF
• β-thalassemia
• hemoglobin E
• globin
• genetic factor

Acknowledgments

This work was supported by Mahidol University Research Grants, Office of the Higher Education Commission and Mahidol University under the National Research University Initiative, and the Research Chair Grant, National Science and Technology Development Agency (NSTDA), Thailand. O.S. was supported by the Thailand Research Fund.

Declaration of interest

O. Sripichai was supported by the Thailand Research Fund. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This work was supported by Mahidol University Research Grants, Office of the Higher Education Commission and Mahidol University under the National Research University Initiative, and the Research Chair Grant, National Science and Technology Development Agency (NSTDA), Thailand.