Schrier S L
Stanford University School of Medicine, Department of Hematology, CA 94305, USA.
Curr Opin Hematol. 1997 Mar;4(2):75-8. doi: 10.1097/00062752-199704020-00001.
Although study of the thalassemias has focussed on possible cure or amelioration by genetic techniques, considerable progress has been made in understanding the underlying pathobiology of these diseases. Better control of childhood infectious diseases has led to a clearer understanding of the frequency and clinical severity of some of these disorders. The striking differences between alpha- and beta-thalassemia are now well documented and the role of oxidant attack in the pathobiology is becoming clearer. Some authors believe that severe beta-thalassemia induces a hypercoagulable state that could be partially caused by scrambling of the phospholipid bilayer of affected erythrocytes. There is growing appreciation that double heterozygosity for hemoglobin E/beta-thalassemia, while causing variable anemia, can produce a clinical condition as severe as Cooley's anemia (beta-thalassemia major). Anemia severity may be related to the extent of oxidant attack on the unstable hemoglobin E. Studies of the hemoglobin Constant Spring variants demonstrate the consequences of accumulating excess unmatched beta globin as well as the unique alpha CS. Studies on marrow erythroid precursors in the beta-thalassemias have already shown accelerated programmed cell death and abnormal assembly of membrane proteins. Such studies in the future will likely further delineate the underlying differences between alpha- and beta-thalassemias.
尽管地中海贫血的研究主要集中在通过基因技术实现可能的治愈或改善，但在理解这些疾病的潜在病理生物学方面已经取得了相当大的进展。对儿童传染病的更好控制使得对其中一些疾病的发病率和临床严重程度有了更清晰的认识。α地中海贫血和β地中海贫血之间的显著差异现在已有充分记录，氧化应激在病理生物学中的作用也越来越清晰。一些作者认为，重型β地中海贫血会导致高凝状态，这可能部分是由受影响红细胞磷脂双分子层的紊乱引起的。人们越来越认识到，血红蛋白E/β地中海贫血的双重杂合性虽然会导致不同程度的贫血，但可能产生与库利贫血（重型β地中海贫血）一样严重的临床症状。贫血的严重程度可能与不稳定血红蛋白E受到的氧化应激程度有关。对血红蛋白恒河猴变体的研究表明了累积过量不匹配的β珠蛋白以及独特的αCS的后果。对β地中海贫血患者骨髓红系前体细胞的研究已经显示出程序性细胞死亡加速和膜蛋白组装异常。未来的此类研究可能会进一步阐明α地中海贫血和β地中海贫血之间的潜在差异。
