Adult and Fetal Hemoglobin Production in Erythroid Colonies from Subjects with β-Thalassemia or with Hereditary Persistence of Fetal Hemoglobin (HPFH)

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