This graph is taken from a study by Goldberg, et al. (N Engl J Med, 1990) in which patients were placed on hydroxyurea for at least one year. The percentage of fetal hemoglobin in the cells as well as the percentage of F-cells were assessed over this period of time. The patients were treated briefly with erythropoietin alone (the horizontal stippled bar) before starting on hydroxyurea. The data are from one individual.
Both the percentage of fetal hemoglobin in the cells as well as the percentage F-cells increased by about two-fold. The number of hospitalizations dropped subtantially for this patient. Hydroxyurea inhibits the enzyme ribonucleotide reductase which is essential for cell division. The drug induces fetal hemoglobin synthesis, although the mechanism is still unknown. One idea is that the drug intermittently blocks the maturation of early normoblasts (BFU-E's). When released from maturational arrest, the BFU-E's (which have a greater capacity to produce hemoglobin F than do cells later in the maturation pathway, short-cut to late normoblasts and eventually red cells that contain a greater fraction of hemoglobin F than would be seen otherwise.
This concept is consistent with the fact that other drugs that interfere with normoblast maturation produce the same effect. Some, such as 5-azacytadine and cytosine arabinocide, are too toxic for use in humans. Hydroxyuea appears to work similarly, but without the inordinate toxicity of the aforementioned powerful chemotherapy agents.