Adult and fetal hemoglobin production in erythroid colonies from subjects with β-thalassemia or with hereditary persistence of fetal hemoglobin (HPFH)

Abstract

The synthesis of α and non-α chains (β, δ, Gγ and Aγ) was studied in cultures of peripheral blood mononuclear cells from eleven β-thalassemia heterozygotes, two HPFH heterozygotes, and one HPFH homozygote. The synthesis of Hb F in the thalassemia colonies (average value: 12.6%) was comparable to that in normal adult colonies (average value: 12.2%). The percent Gγ chain in the Hb F varied greatly but a relationship between the Gγ chain percentage in the Hb F from colonies and that from peripheral blood was established. The relative synthesis of Hb A2 in colonies of β-thalassemia heterozygotes (average value: 5.8%) was 1.6 times as much as that in colonies of normal adults (average value: 3.6%). Hb A2 and Hb A were absent in the colonies of the HPFH homozygote. The α/non-α (i.e., β, γ, and δ) ratio of the hemoglobins in the cultured cells of the β-thalassemia heterozygotes and the α/β and α/δ ratios of isolated Hb A and Hb A2 were about one (range 0.74 to 1.38). The α/γ ratio of the Hb F synthesized in BFUe-derived colonies of the HPFH homozygote, however, was 1.5. The results suggest a deficiency in the in vitro culture system resulting in decreased levels of α-mRNA or in a partial inhibition of initiation of protein synthesis which is known to reduce the synthesis of α chains more than that of the β chains.