Influence of hydroxyurea on fetal hemoglobin production in vitro

Barbara Miller, O. Platt, S. Hope, G. Dover, D. G. Nathan

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 μmol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 μmol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.

Original languageEnglish (US)
Pages (from-to)1824-1829
Number of pages6
JournalBlood
Volume70
Issue number6
StatePublished - Dec 1 1987

Fingerprint

Fetal Hemoglobin
Erythroid Precursor Cells
Hydroxyurea
Erythroblasts
Blood
Bone
Bone Marrow
In Vitro Techniques
Erythropoiesis
Reticulocytes
Sickle Cell Anemia
Blood Donors
Haplorhini
Tissue Donors
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Miller, B., Platt, O., Hope, S., Dover, G., & Nathan, D. G. (1987). Influence of hydroxyurea on fetal hemoglobin production in vitro. Blood, 70(6), 1824-1829.
Miller, Barbara ; Platt, O. ; Hope, S. ; Dover, G. ; Nathan, D. G. / Influence of hydroxyurea on fetal hemoglobin production in vitro. In: Blood. 1987 ; Vol. 70, No. 6. pp. 1824-1829.
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Miller, B, Platt, O, Hope, S, Dover, G & Nathan, DG 1987, 'Influence of hydroxyurea on fetal hemoglobin production in vitro', Blood, vol. 70, no. 6, pp. 1824-1829.

Influence of hydroxyurea on fetal hemoglobin production in vitro. / Miller, Barbara; Platt, O.; Hope, S.; Dover, G.; Nathan, D. G.

In: Blood, Vol. 70, No. 6, 01.12.1987, p. 1824-1829.

Research output: Contribution to journalArticle

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T1 - Influence of hydroxyurea on fetal hemoglobin production in vitro

AU - Miller, Barbara

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AU - Dover, G.

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N2 - Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 μmol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 μmol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.

AB - Cytotoxic drugs increase circulating fetal hemoglobin levels. We examined the mechanism by measuring the fetal hemoglobin produced per BFU-E-derived erythroblast following hydroxyurea treatment in vivo and in vitro. Treatment of four sickle cell patients increased the percentage of circulating F reticulocytes. The frequencies of bone marrow or peripheral blood BFU-E or CFU-E-derived colonies and their fetal hemoglobin content were unaffected. In all cases, the number of erythroid cells/progenitor-derived colony increased. To explore further the effect of hydroxyurea on fetal hemoglobin production, we added 50 μmol/L hydroxyurea to cultures of peripheral blood BFU-E-derived erythroblasts on 1 of 9 days (day 5 through 13) to nine samples. These BFU-E were derived from the peripheral blood of normal donors, sickle trait donors, and sickle cell anemia patients and from the bone marrows of monkeys. This concentration of hydroxyurea was selected so that the frequency of BFU-E and their size was moderately decreased. Addition of hydroxyurea to these progenitor-derived erythroid cells had no effect on fetal hemoglobin content per cell. Neither did transient exposure of progenitors to hydroxyurea prior to culture in nontoxic concentrations (0 to 500 μmol/L) result in a significant increase in fetal hemoglobin content in progenitor-derived erythroblasts. These data suggest that hydroxyurea does not directly alter the HbF program expressed by progenitor-derived erythroid cells. Instead, it enhances hemoglobin F content secondarily, possibly by inducing alterations in erythropoiesis.

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Miller B, Platt O, Hope S, Dover G, Nathan DG. Influence of hydroxyurea on fetal hemoglobin production in vitro. Blood. 1987 Dec 1;70(6):1824-1829.