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Hydroxyurea-induced HbF production in anemic primates: augmentation by erythropoietin, hematopoietic growth factors, and sodium butyrate.
Exp Hematol 1992; 20(10):1156-64EH

Abstract

Hydroxyurea, a cell-cycle-specific cytotoxic agent, has been shown to increase fetal hemoglobin (HbF) production. This property makes it an attractive drug for treatment of sickle cell disease and severe beta thalassemia. Its potential efficacy is limited because of a variable and often suboptimal response. Combinations of hydroxyurea and other drugs may induce more clinically significant increases in HbF. We have utilized chronically phlebotomized rhesus monkeys, treated with oral hydroxyurea, to investigate the capacity of several other agents to further augment HbF synthesis. Recombinant human erythropoietin, in super-pharmacologic doses, increased F-reticulocyte production when given on a weekly sequential schedule (3 of 7 days) with hydroxyurea (4 of 7 days), but it was less effective on an alternate day schedule when hydroxyurea was given daily. Neither recombinant human interleukin 3 (IL-3) nor recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), when infused individually, increased F-reticulocytes in animals receiving daily hydroxyurea. Sequential, overlapping infusions of IL-3 and GM-CSF produced a small but statistically significant increase in F-reticulocytes in one of two hydroxyurea-treated animals. Infusions of sodium butyrate produced a substantial augmentation in F-reticulocyte production in animals chronically treated with hydroxyurea. Thus, our studies have identified several agents that may prove useful in combination with hydroxyurea to achieve clinically beneficial levels of HbF.

Authors+Show Affiliations

Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1385194

Citation

McDonagh, K T., et al. "Hydroxyurea-induced HbF Production in Anemic Primates: Augmentation By Erythropoietin, Hematopoietic Growth Factors, and Sodium Butyrate." Experimental Hematology, vol. 20, no. 10, 1992, pp. 1156-64.
McDonagh KT, Dover GJ, Donahue RE, et al. Hydroxyurea-induced HbF production in anemic primates: augmentation by erythropoietin, hematopoietic growth factors, and sodium butyrate. Exp Hematol. 1992;20(10):1156-64.
McDonagh, K. T., Dover, G. J., Donahue, R. E., Nathan, D. G., Agricola, B., Byrne, E., & Nienhuis, A. W. (1992). Hydroxyurea-induced HbF production in anemic primates: augmentation by erythropoietin, hematopoietic growth factors, and sodium butyrate. Experimental Hematology, 20(10), pp. 1156-64.
McDonagh KT, et al. Hydroxyurea-induced HbF Production in Anemic Primates: Augmentation By Erythropoietin, Hematopoietic Growth Factors, and Sodium Butyrate. Exp Hematol. 1992;20(10):1156-64. PubMed PMID: 1385194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxyurea-induced HbF production in anemic primates: augmentation by erythropoietin, hematopoietic growth factors, and sodium butyrate. AU - McDonagh,K T, AU - Dover,G J, AU - Donahue,R E, AU - Nathan,D G, AU - Agricola,B, AU - Byrne,E, AU - Nienhuis,A W, PY - 1992/11/1/pubmed PY - 1992/11/1/medline PY - 1992/11/1/entrez SP - 1156 EP - 64 JF - Experimental hematology JO - Exp. Hematol. VL - 20 IS - 10 N2 - Hydroxyurea, a cell-cycle-specific cytotoxic agent, has been shown to increase fetal hemoglobin (HbF) production. This property makes it an attractive drug for treatment of sickle cell disease and severe beta thalassemia. Its potential efficacy is limited because of a variable and often suboptimal response. Combinations of hydroxyurea and other drugs may induce more clinically significant increases in HbF. We have utilized chronically phlebotomized rhesus monkeys, treated with oral hydroxyurea, to investigate the capacity of several other agents to further augment HbF synthesis. Recombinant human erythropoietin, in super-pharmacologic doses, increased F-reticulocyte production when given on a weekly sequential schedule (3 of 7 days) with hydroxyurea (4 of 7 days), but it was less effective on an alternate day schedule when hydroxyurea was given daily. Neither recombinant human interleukin 3 (IL-3) nor recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), when infused individually, increased F-reticulocytes in animals receiving daily hydroxyurea. Sequential, overlapping infusions of IL-3 and GM-CSF produced a small but statistically significant increase in F-reticulocytes in one of two hydroxyurea-treated animals. Infusions of sodium butyrate produced a substantial augmentation in F-reticulocyte production in animals chronically treated with hydroxyurea. Thus, our studies have identified several agents that may prove useful in combination with hydroxyurea to achieve clinically beneficial levels of HbF. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/1385194/Hydroxyurea_induced_HbF_production_in_anemic_primates:_augmentation_by_erythropoietin_hematopoietic_growth_factors_and_sodium_butyrate_ L2 - https://medlineplus.gov/anemia.html DB - PRIME DP - Unbound Medicine ER -