Evaluation of H3 histone methylation and colony formation in erythroid progenitors treated with thalidomide and sodium butyrate.

OBJECTIVES

β-thalassemia and sickle cell disease are hemoglobinopathies with reduced/absent β chains in the former and dysfunctional β chains in the latter. In both conditions, up-regulation of hemoglobin F through demethylation can alleviate the symptoms. This can be attained with drugs such as thalidomide and sodium butyrate.

MATERIALS AND

METHODS

This study was performed on erythroid progenitors derived from CD133+ cord blood stem cells. Erythroid progenitors were treated with thalidomide and sodium butyrate in single and combined groups. Colony-formation potential in each group was evaluated by the colony assay. Real-time polymerase chain reaction (RT-PCR) was used to evaluate the effect of these drugs on histone H3 lysine 27 (H3K27) methylation patterns.

FINDINGS: Compared to other treatment groups, CD133+ cells treated with thalidomide alone produced more hematopoietic colonies. Thalidomide alone was also more effective in decreasing H3K27 methylation.

CONCLUSIONS

Thalidomide shows superiority to sodium butyrate as a hypomethylating agent in this cell culture study, and it has the potential to become conventional treatment for sickle cell disease and β-thalassemia.