Evaluation of Novel Fetal Hemoglobin Inducer Drugs in Treatment of β-Hemoglobinopathy Disorders

Abstract

Objective: The use of fetal hemoglobin (HbF) inducer drugs is considered as a novel approach in treatment of β-hemoglobinopathies, especially β- thalassemia and sickle cell disease. HbF inducers including hydroxyurea, histone deacetylase (HDAC) inhibitor agents such as sodium butyrate, azacitidine, decitabine and new immunomodulator drugs like pomalidomide, lenalidomide and thalidomide can reduce α-globin chain production in erythroid progenitors and improve α: β chain imbalance, the most crucial complication of β-thalassemia.

Materials and methods: In this article, we reviewed more than 40 articles published from 1979 to 2012 in the field of fetal hemoglobin augmentation.

Results: Recent studies suggest the synergistic effect of drug combinations in efficient induction of fetal hemoglobin and gene over-expression.

Conclusion: It seems that drugs which act with different molecular and epigenetic mechanisms have proper synergistic effects in fetal hemoglobin induction and gene over-expression.

Keywords: Fetal hemoglobin; Histone deacetylase; β-Hemoglobinopathies.

Figure 1

Drugs and their induction mechanism of γ-globin gene. For details refer to text Abbreviation: EPO, erythropoietin; HU, hydroxyurea; SCF, stem cell factor; NO, nitric oxide; ROS, reactive oxygen species; P38 MAPK, p38 mitogen activation protein kinase; CH3, methyl group; HAT, histone acetyl transferase; HDAC, histone deacetylase; DNMT, DNA methyl transferase; AC, acetyl group; SAHA, suberoylanilide hydroxaminc acid.