title: Globin biosynthesis in erythroid bursts of heterozygous alpha or beta thalassaemia.
abstract: We examined globin chain synthesis in erythroid bursts (BFU-E) of patients with heterozygous alpha or beta thalassaemia. BFU-E were cloned from circulating mononuclear cells, labelled with [3H]leucine and globin chains purified by gel filtration and column chromatography. In six patients heterozygous for beta thalassaemia, 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 anaemia (25.6 +/- 6.7) but greater (P > 0.05) than that of five normal controls (17.2 +/- 2.2). The balanced globin synthesis appeared due to the large amounts of gamma chain made by BFU-E. In two alpha thalassaemia carriers, who also had sickle cell trait, the BFU-E alpha/non-alpha ratio was 0.67 and 0.79. These BFU-E produced 15% and 20% gamma chain and 39% and 45% betaS globin. The synthesis of betaS globin in BFU-E exceeded the erythrocyte levels of 20% and 29% HbS and indicated nearly equal expression of betaA and betaB globin genes in these proliferating erythroid precursors. This provides further evidence that the low levels of HbS in sickle cell carriers with alpha thalassaemia are due to post-translational events resulting from the differing affinity of betaS and betaA globin for alpha chain and the destruction of excessive betaS chain.
mesh_terms: D001772:Blood Cell Count; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005914:Globins / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006454:Hemoglobins / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D012156:Reticulocytes / Q000378:metabolism; D013789:Thalassemia / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D005914:Globins