"Over-expression of AHSP in Bone Marrow - derived CD34+ cells is not effective in ameliorating the thalassemic phenotype"

Abstract

Sox6 belongs to the Sry-related HMG-box family of transcription factors, which control cell fate specification of many cell types. Here we explore the role of Sox6 in human erythropoiesis by its over-expression in both the erytholeukemic K562 cell line and in primary erythroid cultures from human cord blood CD34+ cells. Sox6 induces significant erythroid differentiation in both models: K562 cells undergo hemoglobinization and, despite their leukemic origin, die within 9 days after transduction; primary erythroid cultures accelerate their kinetic of erythroid maturation and increase the number of cells reaching the final enucleation step. Searching for direct Sox6 targets, we found SOCS3 (Suppressor of Cytokine signalling-3), a known mediator of cytokine response. Sox6 binds in vitro and in vivo to an evolutionary conserved regulatory SOCS3 element, inducing transcriptional activation. SOCS3 overexpression in K562 cells and in primary erythroid cells recapitulates the growth inhibition induced by Sox6, demonstrating that SOCS3 is a relevant Sox6 effector. The Sox6-mediated SOCS3 induction is, in K562, accompanied by a decreased expression of IGF-1 gene, a known inhibitor of apoptosis and survival factor for hematopoietic cells.