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RNA from bone marrow erythroblasts and peripheral blood reticulocytes of patients with heterozygous beta-thalassemia was analyzed for relative content of alpha and beta globin messenger RNA by molecular hybrization. Erythroblasts from nonthalassemic patients exhibited approximately the same alpha and beta globin mRNA content (beta/alpha mRNA ratio = 0.8-1.0) as circulating reticulocytes (beta/alpha mRNA ratio = 0.74-1.2). The mRNA ratios corresponded well to levels of globin synthesis observed in bone marrow and peripheral blood. Erythroblasts from four patients with heterozygous beta-thalassemia also exhibited approximately the same beta/alpha mRNA ratios in bone marrow erythroblasts (0.34-0.59) as in reticulocytes (0.34-0.4): beta globin mRNA was clearly deficient in bone marrow erythroblasts. Globin biosynthesis by erythroblasts of beta-thalassemia heterozygotes was balanced despite the mRNA deficiency (beta/alpha = 0.9-1.0), suggesting that post-translational phenoma (eg, proteolysis of free globin chains), rather than instability of beta mRNA, accounts for the balanced globin chain synthesis frequently observed in bone marrow erythroblasts of patients with beta-thalassemia trait.
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