Differences in response to fetal hemoglobin induction therapy in β-thalassemia and sickle cell disease
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- 作者：Hassana Fathallah ; Ali Taher ; Ali Bazarbachi ; George F. Atweh
- 关键词：Thalassemia ; Sickle cells ; Hemoglobin expression ; Butyrate ; Hemin
- 刊名：Blood Cells, Molecules, and Diseases
- 出版年：2009
- 出版时间：July-August 2009
- 年：2009
- 卷：43
- 期：1
- 页码：58-62
- 全文大小：558 K
文摘
Inducers of fetal hemoglobin (HbF) have shown considerable promise in the treatment of sickle cell disease (SCD). However, the same agents have shown less clinical activity in β-thalassemia (β-Thal). To understand the basis of these differences in clinical effectiveness, we compared the effects of butyrate and hemin on the expression of the different globin genes in progenitors-derived erythroid cells from patients with β-Thal intermedia and SCD. Exposure to butyrate resulted in an augmentation of γ-globin mRNA levels in both SCD and β-Thal. Interestingly, butyrate exposure increased α-globin expression in β-Thal, while α-globin mRNA levels decreased in SCD in response to butyrate. As a result, the favorable effects of the butyrate-induced increase in γ-globin expression on α:β-like globin mRNA imbalance in β-Thal were reduced as a result of the associated increase in α-globin expression. Hemin had similar but less profound effects on all three globin genes in both categories of patients. Although the majority of patients with β-Thal did not correct their globin imbalance in response to butyrate or hemin induction of HbF in a minority of patients resulted in marked reduction in globin imbalance. Thus, we believe that the poor clinical response in a majority of patients with β-Thal to inducers of γ-globin expression may be a reflection of unfavorable effects of these agents on the other globin genes.