Decreased alpha globine mRNA in nucleated red cell precursors in alpha
thalassemia
CL Natta, F Ramirez, JA Wolff and A Bank
The alpha thalassemias are associated with a decrease in alpha chain
synthesis. Hemoglobin H (HbH) disease is a moderately severe form of alpha
thalassemia characterized by the production of 5%--20% of HbH, while alpha
thalassemia trait is a milder form of alpha thalassemia. In two patients
with HbH disease, the ratio of alpha chain synthesis to beta chain
synthesis (alpha/beta 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 alpha/beta 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 alpha and beta cDNA probes. In the intact cells of two patients
with alpha thalassemia trait, the alpha/beta ratios were also decreased and
were similar in marrow cells and reticulocytes. Cell-free studies of
translatable mRNA also demonstrated decreased alpha/beta ratios, but,
unlike the HbH studies, the cell-free alpha/beta ratios were similar to the
intact cell ratios. One hybridization study utilizing peripheral blood mRNA
had an alpha/beta ratio consistent with the cell-free ratios. These results
indicated that, in both HbH disease and alpha thalassemia trait, there was
decreased alpha 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 alpha thalassemia trait cells, no such
controls appeared to be active and globin chain synthesis was directly
proportional to the amount of alpha and beta globin mRNA in the cells.
Volume 47,
Issue 6,
pp. 899-907,
06/01/1976
Copyright © 1976 by The American Society of Hematology
