Summary of the unbalanced globin/heme equilibrium in DBA and the rescue of erythroid proliferation and differentiation by overexpression of HSP70.⁹⁸  (A) During normal erythropoiesis, globin chains and heme are stoichiometrically expressed to produce Hb with no excess heme. (B) In DBA-affected patients who carry a mutation in the RPL5 or RPL11 gene, there is disequilibrium between globin and heme synthesis, resulting in excess free heme in erythroid cells. The excess free heme results in increased reactive oxygen species (ROS) production, contributing to cell death in DBA. (C) Overexpression of HSP70 rescues the DBA phenotype by protecting GATA1 and restoring globin/heme balance and thereby rescuing the erythroid proliferation and differentiation by decreasing apoptosis and erythroid cell death.