Weill Medical College of Cornell University, New York, NY, USA.
Blood Rev. 2012 Apr;26 Suppl 1(0 1):S12-5. doi: 10.1016/S0268-960X(12)70005-X.
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.
无效造血是β-地中海贫血的标志，它引发了一系列代偿机制，导致临床后果，如红系骨髓扩张、髓外造血、脾肿大和胃肠道铁吸收增加。最近的研究开始揭示无效造血和相关代偿途径背后的复杂分子机制；这种新的认识可能会导致新疗法的发展。Jak2/STAT5 通路的过度激活或过度激活会促进红细胞祖细胞的不必要的不成比例的过度增殖，而其他因素会抑制血清铁调素水平，导致铁代谢失调。临床前研究表明，Jak 抑制剂、铁调素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，并减少脾肿大；然而，还需要进一步的研究。
