Romidepsin and Simvastatin Induce Gamma Globin Gene

Induction of HbF as stable clinical effect for beta thalassemia and sickle cell anemia treatment is most promising approach. Using HbF inducer drugs is cost effective, easy access and safe, compare to other approaches for these hemoglobinopathies treatment. At the present study we used Simvastatin and Romidepsin for evaluation HbF induction in erythroid progenitors differentiated from cord blood stem cells. Our research was an experimental study that isolated CD34+ Cells from five cord bloods were cultured in erythroid differentiation medium containing Romidepsin and Simvastatin. The results of colony assay and erythroid markers such as CD36 and CD71 confirmed that the isolated cells can differentiate to erythroid commitment cell. Gamma globin, BCL11a and HDAC gene expression were evaluated on 7th and 14th day of erythroid differentiation by Real-time PCR and HbF production was evaluated by Immunofluorescence staining on 14th day of differentiiation. Our results showed that Simvastatin and Romidepsin Increase gamma globin expression 1.37 and 1.78 respectively (P<0.05).But combination of Simvastatin and Romidepsin increased gamma globin expression 3.09-fold over the control group synergistically (P<0.05).Our results showed which HbF Induction of mentioned drugs is done by HDAC1 and BCL11a inhibition as two important inhibitors for HbF production after birth. We propose combination therapy of these drugs ameliorate clinical manifestation in beta thalassemia and SCD with at least side effect and reduce the need for blood transfusion.

کلیدواژه ها:

Simvastatin ، Romidepsin ، beta thalassemia ، sickle cell disease. HDAC1/2 ، BCL11a