Decreased a Globin mRNA in Nucleated Red Cell Precursors in a Thalassemia

The a thalassemias are associated with a decrease in a chain synthesis. Hemoglobin H (HbH) disease is a moderately severe form of a thalassemia characterized by the production of 5%-20% of HbH, while a thalassemia trait is a milder form of a thalassemia. In two patients with HbH disease, the ratio of a chain synthesis to fi chain synthesis (a/fl ratio) was decreased in both bone marrow cells and reticulocytes. When isolated mRNA from bone marrow cells and reticulocytes was translated in a heterologous cell-free system, the a/fl ratios were lower than the intact cell ratios. These findings were confirmed by hybridization of the mRNA of both marrow cells and reticulocytes using purified a and l cDNA probes. In the intact cells of two patients with a thaIassemia trait, the a/el ratios were also decreased and were similar in marrow cells and reticulocytes. Cell-free studies of translatable mRNA also demonstrated decreased a/fl ratios, but, unlike the HbH studies, the cell-free a/fl ratios were similar to the intact cell ratios. One hybridization study utilizing peripheral blood mRNA had an a/fl ratio consistent with the cell-free ratios. These results indicated that, in both HbH disease and a thalassemia trait, there was decreased a globin mRNA present in both nucleated red cell precursors and reticulocytes. In addition, the data suggested that there may be translational mechanisms that operate in intact HbH cells which attempt to balance globin chain production. In a thalassemia trait cells, no such controls appeared to be active and globin chain synthesis was directly proportional to the amount of a and fi globin mRNA in the cells.