Effects of rapamycin on accumulation of α-, β- and γ-globin mRNAs in erythroid precursor cells from β-thalassaemia patients
Effects of rapamycin on accumulation of α-, β- and γ-globin mRNAs in erythroid precursor cells from β-thalassaemia patients
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DOI：
10.1111/j.1600-0609.2006.00731.x
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Gambari, Roberto
中科院分区：
文献类型：
--
作者：
Fibach, Eitan;Bianchi, Nicoletta;Gambari, Roberto
我们研究了雷帕霉素对10例β-地中海贫血患者外周血红系祖细胞培养的影响，这些患者产生胎儿血红蛋白（HbF）的潜力差异很大。为此，我们采用两相液体培养程序生长的红系祖细胞，高效液相色谱分析的HbF生产和逆转录聚合酶链反应的珠蛋白mRNA的积累进行定量。结果表明，雷帕霉素诱导所有β-地中海贫血患者的培养物中HbF增加，以及他们的总Hb含量/细胞增加。雷帕霉素的诱导作用仅限于γ-珠蛋白mRNA的积累，β-珠蛋白mRNA的诱导作用很小，α-珠蛋白mRNA的诱导作用不明显。雷帕霉素优先增加来自β-地中海贫血患者的红系前体细胞中的γ-珠蛋白mRNA含量和HbF产生的能力是非常重要的，因为这种药剂（也称为西罗莫司或雷帕霉素）已经在临床上用作肾移植后的抗排斥剂。这些数据表明，雷帕霉素值得进一步评估作为一种潜在的治疗药物在β地中海贫血和镰状细胞贫血。
We studied the effects of rapamycin on cultures of erythroid progenitors derived from the peripheral blood of 10 beta-thalassaemia patients differing widely with respect to their potential to produce foetal haemoglobin (HbF). For this, we employed the two-phase liquid culture procedure for growing erythroid progenitors, high performance liquid chromatography for analysis of HbF production and reverse transcription polymerase chain reaction for quantification of the accumulation of globin mRNAs. The results demonstrated that rapamycin induced an increase of HbF in cultures from all the beta-thalassaemia patients studied and an increase of their overall Hb content/cell. The inducing effect of rapamycin was restricted to gamma-globin mRNA accumulation, being only minor for beta-globin and none for alpha-globin mRNAs. The ability of rapamycin to preferentially increase gamma-globin mRNA content and production of HbF in erythroid precursor cells from beta-thalassaemia patients is of great importance as this agent (also known as sirolimus or rapamune) is already in clinical use as an anti-rejection agent following kidney transplantation. These data suggest that rapamycin warrants further evaluation as a potential therapeutic drug in beta-thalassaemia and sickle cell anaemia.