CONSISTENT ACTIVATION OF FETAL HEMOGLOBIN SYNTHESIS IN CULTURED ADULT BONE-MARROW CELLS

Abstract

The production of fetal Hb (HbF) was investigated in [human] plasma clot cultures of adult bone marrow cells from normal donors and from individuals with homozygous HbS or HbC disease. Synthesis of .gamma. and .beta. chains was assessed by 35S-methionine labeling cultures and measurement of the radioactivity incorporated into the methionine-containing tryptic peptides of the .gamma. and .beta. subunits or by 3H-leucine labeling and measurement of the radioactivity incorporated into the globin chains of HbF0 and HbA0 isolated by ion-exchange chromatography. The cultures from all individuals responded with increased production of HbF. Cultured cells from subjects without a hemoglobinopathy produced an average of 8.2% .gamma. chains (range 3.1%-20.3%), while cultured cells from subjects homozygous for HbS or HbC produced an average of 16.6% .gamma. chains (range 12.2%-20.4%). HbF production was probab ly regularly enhanced in adult bone marrow cells triggered in vitro to clonal growth in the plasma clot culture system.