The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia.
The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia.
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DOI：
10.1016/s0268-960x(12)70005-x
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发表时间：
2012-04
期刊：
影响因子：
7.4
通讯作者：
Rivella, Stefano
中科院分区：
文献类型：
--
作者：
Rivella, Stefano
无效的红细胞生成是β-地中海贫血的特征，它触发一系列代偿机制，导致临床后遗症，如红系骨髓扩张、髓外造血、脾肿大和胃肠道铁吸收增加。最近的研究已经开始阐明无效的红细胞生成及其相关的代偿途径背后的复杂分子机制；这一新的理解可能导致新疗法的发展。JAK2/STAT5通路的高激活或过度激活促进了红系祖细胞不必要的不成比例的增殖，而其他因素抑制了血清中的海普西丁水平，导致铁代谢的失调。临床前研究表明，JAK抑制剂、海普西丁激动剂和外源性转铁蛋白可能有助于恢复正常的红细胞生成和铁代谢，减少脾肿大；然而，还需要进一步的研究。
Ineffective erythropoiesis is the hallmark of beta-thalassemia that triggers a cascade of compensatory mechanisms resulting in clinical sequelae such as erythroid marrow expansion, extramedullary hematopoiesis, splenomegaly, and increased gastrointestinal iron absorption. Recent studies have begun to shed light on the complex molecular mechanisms underlying ineffective erythropoiesis and the associated compensatory pathways; this new understanding may lead to the development of novel therapies. Increased or excessive activation of the Jak2/STAT5 pathway promotes unnecessary disproportionate proliferation of erythroid progenitors, while other factors suppress serum hepcidin levels leading to dysregulation of iron metabolism. Preclinical studies suggest that Jak inhibitors, hepcidin agonists, and exogenous transferrin may help to restore normal erythropoiesis and iron metabolism and reduce splenomegaly; however, further research is needed.