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  • Title: Imbalanced globin chain synthesis in heterozygous beta-thalassemic bone marrow.
    Author: Chalevelakis G, Clegg JB, Weatherall DJ.
    Journal: Proc Natl Acad Sci U S A; 1975 Oct; 72(10):3853-7. PubMed ID: 1060068.
    Abstract:
    Globin synthesis was studied in the bone marrow of seven heterozygous beta-thalassemic subjects. We found evidence of significant imbalance of alpha- and beta-chain production particularly at short times of incubation. There was a progressive decrease in alpha/beta-chain production ratio with increasing incubation time which was due to a decreased rate of net alpha-chain production, indicating that a large proportion of the newly synthesized alpha chains are degraded, particularly in bone marrow, within a few minutes of synthesis, leading to relatively low alpha/beta ratios if these are measured solely at incubation times greater than 10 min. The significant degradation of excess alpha chains explains why inclusion body formation and ineffective erythropoiesis, notable in beta-thalassemia homozygotes where there is gross chain imbalance, are not observed to any marked degree in heterozygotes.
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