Fetal hemoglobin biosynthesis in clonal cell culture.

Availability of the clonal erythropoietic cell culture methods provided a unique opportunity to study human hemoglobin biosynthesis under controlled conditions. Observations in several laboratories during the last four years fundamentally agree and can be summarized as follows: (1) Biosynthesis of fetal hemoglobin (HbF) is markedly augmented in cultures of adult erythropoietic precursors. (2) HbF biosynthetic capabilities inversely parallel the maturational stages of adult erythropoietic precursors in the marrow. (3) Adult circulating precursors (BFU-e) are also capable of augmented HbF biosynthesis in culture. (4) The pattern of Hb synthesized by fetal erythropoietic precursors corresponds very closely to the Hb compositions in the mature erythrocytes of the donors. (5) Burst-promoting activities (BPA) rather than erythropoietin (Ep) appear to stimulate HbF biosynthesis by augmentation of proliferation of precursors which are programmed to produce F cells in vivo. (6) Individual BFU-e are heterogeneously committed to HbF biosynthesis and their frequency distributions reveal normal distributions. (7) Increase in HbF production in culture is primarily due to increased production of the number of cells containing Hbf. (8) Commitment to produce HbF continues during subcolony formation in culture. (9)HbF synthesized in culture of adult and umbilical cord blood BFU-e reveal "adult" and "intermediate" values of G gamma:A gamma ratios, respectively. (1)) Frequency distributions of individual bursts varying in relative G gamma synthesis (G gamma/[G gamma+A gamma]) reveal unimodal distributions. (11) Positive correlations exist between gamma/(gamma+beta) and G gamma/(G gamma + A gamma) values in individual bursts.