IFN-γ/JAK/STAT axis awakens the delta force of hemoglobin

In this issue of Blood, Zhu et al 1 demonstrated that treatment of interferon gamma (IFN-) produced a significant activation of HBD gene transcription via STAT1/3 phosphorylation and adult hemoglobin A 2 (HbA 2 ) induction in a model erythroid cell line, normal-and sickle-derived erythroid progenitors.Therapeutically, to increase levels of nonsickling hemoglobin, efforts have been directed toward pharmacological fetal hemoglobin (HbF, 2 2 ) induction to reduce disease severity, whereas far less is known about how the HBD globin gene could be explored.This study critically assessed HBD induction by IFN- to develop novel treatment strategies for sickle cell disease (SCD) and -thalassemia.