Effects of hydroxurea, stem cell factor, and erythropoietin in combination on fetal hemoglobin in the baboon.
OBJECTIVE
Augmentation of the level of fetal hemoglobin (HbF) is considered therapeutic for patients with sickle cell disease. The objective of this study was to determine the effect of treatment with a combination of erythropoietin (Epo), stem cell factor (SCF), and hydroxyurea (HU) on HbF levels.


METHODS
The effect of treatment with a combination of Epo, SCF, and HU on HbF, F-cell numbers, and globin chain synthesis was evaluated in a baboon model.


RESULTS
Treatment with a combination of SCF+Epo resulted in a two-fold increase in HbF, F-cells, and F-reticulocytes compared to Epo alone. The combination of SCF+Epo+HU resulted in an additional two-fold increase in HbF, whereas F-cells and F-reticulocytes increased only 25% compared to the SCF+Epo regimen. Measurement of differential globin chain synthesis indicated that the SCF+Epo+HU treatment also increased the I gamma/V gamma (homologous to human G gamma and A gamma) synthetic ratio toward the fetal ratio.


CONCLUSIONS
HU can effectively augment growth factor-induced HbF synthesis in vivo. Because I gamma/V gamma ratios are unaffected by erythropoietic stress and similar increases in this ratio have only been observed following administration of 5-azacytidine, we suggest that these two agents may share a common mechanism of action involving the recruitment of a similar target cell population to terminal erythroid differentiation.
Lavelle
D
D
Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA. dlavelle@uic.edu
Molokie
R
R
Ducksworth
J
J
DeSimone
J
J
D000818:Animals; D004347:Drug Interactions; D004906:Erythrocyte Count; D004920:Erythropoiesis; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005914:Globins / Q000096:biosynthesis; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000494:pharmacology*; D010215:Papio; D011994:Recombinant Proteins; D017701:Reticulocyte Count; D019089:Stem Cell Factor / Q000008:administration & dosage / Q000494:pharmacology*
D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D005914:Globins; D005319:Fetal Hemoglobin; D006918:Hydroxyurea