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Cell Journal، جلد ۲۰، شماره ۰۴، صفحات ۵۷۶-۵۸۳
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عنوان انگلیسی Synergistic Effect of Simvastatin and Romidepsin on Gamma-globin Gene Induction
چکیده انگلیسی مقاله Objective: Hemoglobinopathies such as beta thalassemia and sickle cell disease are inheritance disorders that are caused by mutation in beta globin chain. Gamma globin gene reactivation can ameliorate clinical manifestation in thalassemia and SCD. HbF inducer drugs can be promising for treatment of beta thalassemia and SCD patients. Recently it has been shown that Simvastatin and Romidepsin induce HbF. Simvastatin is BCL11a inhibitor and Romidepsin is HDAC inhibitor and both are FDA-approved. Materials and methods: isolated CD34+ Cells from five cord bloods were cultured in erythroid differentiation medium containing Romidepsin and Simvastatin and then gamma globin, BCL11a and HDAC gene expression were evaluated on 7th and 14th day of erythroid differentiation by real-time PCR and Immunocytochemistry. Results: Our results showed that combination of Simvastatin and Romidepsin increased gamma globin expression significantly, and BCL11a and HDAC inhibition were more than when they were used alone. Simvastatin and Romidepsin increased HbF production mean 3.09-fold over the control group. Also Simvastatin inhibited BCL11a expression (0.065-fold) and Romidepsin inhibited HDAC1 expression (0.47-fold) as two important inhibitors for HbF production after birth. Conclusion: 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.
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نویسندگان مقاله | Hussain Habibi


| Amir Atashi


| Saeid Abroun


| Mehrdad Noruzinia


نشانی اینترنتی https://celljournal.org/journal/article/abstract/5589
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