Emerging science of hydroxyurea therapy for pediatric sickle cell disease.

ABSTRACT: Hydroxyurea (HU) is the sole approved pharmacological therapy for sickle cell disease (SCD). Higher levels of fetal hemoglobin (HbF) diminish deoxygenated sickle globin polymerization in vitro and clinically reduce the incidence of disease morbidities. Clinical and laboratory effects of HU largely result from induction of HbF expression, though to a highly variable extent. Baseline and HU-induced HbF expression are both inherited complex traits. In children with SCD, baseline HbF remains the best predictor of drug-induced levels, but this accounts for only a portion of the induction. A limited number of validated genetic loci are strongly associated with higher baseline HbF levels in SCD. For induced HbF levels, genetic approaches using candidate single-nucleotide polymorphisms (SNPs) have

SUBMITTER: Green NS 

PROVIDER: S-EPMC3917141 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature