Effects of dexamethasone on fetal hemoglobin synthesis in peripheral blood erythroid burst-forming units.
Colonies derived from erythroid burst-forming units (BFU-E) synthesize fetal hemoglobin (HbF) in amounts that far exceed in vivo levels. There is some evidence that HbF synthesis is controlled at the level of a primitive erythroid precursor cell. Dexamethasone may potentiate the development of BFU-E. Since a means of augmenting HbF production in sickle cell anemia or severe beta-thalassemia would be of great therapeutic value, we studied the effects of dexamethasone on HbF and gamma-globin chain synthesis in BFU-E from patients with sickle cell anemia and controls. HbF was measured by radioimmunoassay of BFU-E lysate and gamma-chain synthesis by the incorporation of 3H-leucine into globin, which was then purified by gel filtration and column chromatography. Dexamethasone (10(-9) M) produced an increase in the number of BFU-E in 16 of 19 subjects when compared with numbers of BFU-E cultured with only erythropoietin. The individual BFU-E were larger and contained more subcolonies. Dexamethasone did not increase HbF or gamma-chain synthesis, and there was no relationship between proliferation of BFU-E and augmented HbF production. Thus, although dexamethasone augmented the development of erythroid bursts, there was no increment in HbF.
D000755:Anemia, Sickle Cell / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D005914:Globins / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D011498:Protein Precursors / Q000096:biosynthesis; D011863:Radioimmunoassay; D013789:Thalassemia / Q000097:blood
D011498:Protein Precursors; D003907:Dexamethasone; D005914:Globins; D005319:Fetal Hemoglobin