Kim H C, Marks P A, Rifking R A, Maniatis G M, Bank A
Blood. 1976 May;47(5):767-76.
There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24-48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha-globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.
β地中海贫血网织红细胞和有核红细胞中的β珠蛋白生成减少。在本研究中，我们检测了不平衡的珠蛋白合成是否在人类红细胞成熟的所有阶段都有表达。为了确定红细胞成熟过程中早期红细胞的珠蛋白合成模式，已开发出一种使用人类骨髓红细胞前体细胞的体外培养系统。通过使用补体和针对正常人红细胞制备的兔抗血清裂解更成熟的红细胞，从非地中海贫血和地中海贫血患者的人类骨髓中分离出早期红细胞前体细胞（原红细胞和嗜碱性红细胞）。在促红细胞生成素存在的情况下，根据形态学标准和珠蛋白合成增加情况确定，红细胞在液体悬浮培养中可分化和增殖24 - 48小时。在培养过程中，非地中海贫血细胞在红细胞分化的所有阶段，α珠蛋白链与β珠蛋白链合成的比例约为1。在来自四名纯合β地中海贫血患者的细胞中，无论是早期红细胞前体细胞还是在培养成熟过程中，与α珠蛋白合成相比，β珠蛋白合成均减少。这些发现表明，在纯合β地中海贫血中，不平衡的珠蛋白链合成在红细胞成熟的所有阶段都有表达。
