Imbalanced Globin Chain Synthesis in Cultured Erythroid Progenitor Cells From Thalassemic Bone Marrow and Peripheral Blood

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AbstractThe plasma clot culture system was utilized to support the growth of erythroid-committed stem cells from the bone marrow of five patients with homozygous β+-thalassemia and the peripheral blood of one patient doubly heterozygous for β°-thalassemia and Hb Lepore. Addition of erythropoietin to the cultures resulted in abundant colony growth (76–185 CFU-E and 3.5–11 BFU-E/6 × 104 bone marrow cells). Eight BFU-E/105 cells were assayed from the peripheral blood of the β°-thalassemia/Hb Lepore patient. Globin chain synthetic ratios of CFU-E- and BFU-E-derived colonies were determined by CMC column chromatography after labeling of the cultures with 3H-leucine for 24 hr prior to peak growth. Absent or decreased β-globin chain synthesis was observed in all cases; β/α synthetic ratios obtained in culture were quantitatively similar to those obtained in the starting bone marrow or peripheral blood cells. Study of globin chain synthesis in colonies derived from peripheral blood BFU-E of the patient with β°-thalassemia/Hb Lepore demonstrated synthesis of a labeled peak consistent with Lepore 60 chains; a similar labeled peak was barely discernable in the study of the starting peripheral blood. We conclude that thalassemic erythroid progenitor cells express in vitro the same program of abnormal globin chain synthesis as in vivo and that the plasma clot culture technique provides a valuable system for the study of the molecular defect in nucleated thalassemic erythroid cells.