Globin Biosynthesis in Erythroid Bursts of Heterozygous α or β Thalassaemia

Abstract
Globin chain synthesis was examined in erythroid bursts (BFU-E) of patients with heterozygous .alpha.- or .beta.-thalassemia. BFU-E were cloned from circulating mononuclear cells, labeled with [3H]leucine and globin chains purified by gel filtration and column chromatography. In 6 patients heterozygous for .beta.-thalassemia, globin synthesis in BFU-E was nearly balanced, with an .alpha./non-.alpha. ratio of 1.05 .+-. 0.12. These BFU-E produced 33.8 .+-. 12.7% .gamma.-globin chain, an amount similar (P > 0.05) to that found in 10 controls with sickle cell anemia (25.6 .+-. 6.7) but greater (P < 0.05) than that of 5 normal controls (17.2 .+-. 2.2). The balanced globin synthesis appeared due to the large amounts of .gamma.-chain made by BFU-E. In 2 .alpha. thalassemia carriers, who also had sickle cell trait, the BFU-E .alpha./non-.alpha. ratios were 0.67 and 0.79. These BFU-E produced 15% and 20% .gamma.-chain and 39% and 45% .beta.S globin, respectively. The synthesis of .beta.S globin in BFU-E exceeded the erythrocyte levels of 20% and 29% HbS and indicated nearly equal expression of .beta.A and .beta.B globin genes in these proliferating erythroid precursors. The low levels of HbS in sickle cell carriers with .alpha.-thalassemia are due to post-translational events resulting from the differing affinity of .beta.S and .beta.A globin for .alpha. chain and the destruction of excessive .beta.S chain.

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