The in Vitro Synthesis of Hemoglobin by Human Bone Marrow in Thalassemia.

I N THALASSEMIA an inability to form hemoglobin at a normal rate is suggested by the marked degree of erythroid hypochromia in the presence of normal or increased serum iron. On purely theoretical grounds, Rich1 and later Itano2 suggested that in this syndrome there exists a defect in the peptide chains of hemoglobin. This concept was further elaborated by Ingram and co-workers3 who suggested that this decreased rate of synthesis of the peptide chains might be due to either (a) an electrophoretically “silent” structural change within individual peptide chains, or (b) a partial deletion or mumtalion cf a structural gene such that messenger RNA or the complete peptide could not be formed at a normal rate. Quantitative amino acid analysis of isolated peptide chains of hemoglobin from several patients with thalassemia has failed to reveal any abnormal seqtmences.4 Thus, a strumctural change in the amino acid sequence, such as found in Hb S, C, etc., has not been found in thalassemia. On the other hand, if abnormal messenger RNA is prodtmced, this might be expected to attach normally to the polyribosomes which then would be incapable of synthesizing peptide chains at a normal rate (the so-called “constipated ribosomes”). Marks and co-workers have, indeed, recently demonstrated that polyribosomes prepared from thalassemia reticulocytes synthesize globin at a rate lower than that seen in other hemolytic anemias. Furthermore, these workers reported that whereas there was a marked decrease in the rate of synthesis of hemoglobin A, there was no definite change in the rate of synthesis of hemoglobin F, when meastmred in the reticulocyte or ribosomal system. Reticulocytes, however, represent the penultimate stage of erythroid maturation. Globin synthesis is markedly reduced from the rate found in more immature cells7 where the bulk of hemoglobin synthesis occurs. Furthermore, there is no definite evidence that the rate of synthesis of the individual hemoglobins (i.e., Hb A, A2 and F) in the reticulocytes is the same as that rate in the more immature erythroid forms. It is also conceivable that if the messenger RNA for globin synthesis in thalassemia was somewhat less stable than that formed in normal nucleated erythroid cells, reticulocytes in thalas-