The emerging role of fetal hemoglobin induction in non-transfusion-dependent thalassemia

Patients with beta (beta)-thalassemia who have high levels of fetal hemoglobin (HbF) have less severe anemia and are often transfusion-independent. Therefore, augmentation of HbF production has been a longstanding therapeutic objective. Three classes of HbF-inducing agents have been investigated for the treatment of beta-thalassemia including chemotherapeutics, short-chain fatty acid derivatives, and recombinant erythropoietin. These agents have several different mechanisms of action and have been shown to increase total hemoglobin levels by 1-5 g/dL above baseline, but none has been able to sustain the therapeutic levels needed to maintain transfusion independence. Recent findings have provided new insights regarding HbF regulatory pathways, providing new opportunities for derepression of fetal globin gene expression and HbF induction. (C) 2012 Elsevier Ltd. All rights reserved.