Format

Send to

Choose Destination
See comment in PubMed Commons below
Haematologica. 2010 Sep;95(9):1599-603. doi: 10.3324/haematol.2010.023325. Epub 2010 Apr 7.

Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model.

Author information

1
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Abstract

Hydroxyurea has proven clinical efficacy in patients with sickle cell disease. Potential mechanisms for the beneficial effects include fetal hemoglobin induction and the reduction of cell adhesive properties, inflammation and hypercoagulability. Using a murine model of sickle cell disease in which fetal hemoglobin induction does not occur, we evaluated whether hydroxyurea administration would still yield improvements in hematologic parameters and reduce end-organ damage. Animals given a maximally tolerated dose of hydroxyurea that resulted in significant reductions in the neutrophil and platelet counts showed no improvement in hemolytic anemia and end-organ damage compared to control mice. In contrast, animals having high levels of fetal hemoglobin due to gene transfer with a gamma-globin lentiviral vector showed correction of anemia and organ damage. These data suggest that induction of fetal hemoglobin by hydroxyurea is an essential mechanism for its clinical benefits.

PMID:
20378564
PMCID:
PMC2930964
DOI:
10.3324/haematol.2010.023325
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center