OBJECTIVE: Clinical heterogeneity among @entity1 with @entity3458 ( @entity3458 ) is influenced by the amount of fetal hemoglobin (HbF) within circulating erythrocytes. Current pharmacotherapy focuses on increasing HbF in order to reduce @entity2142 and help prevent acute vaso-occlusive events. @entity1862 , a known S-phase-specific cytotoxic @entity2151 reductase (RR) inhibitor, is an effective agent for HbF induction in @entity1 with @entity3458 , but the mechanisms by which @entity1862 induces HbF in vivo have not been elucidated. MATERIALS AND METHODS: We adapted an in vitro assay for HbF induction, growing burst-forming unit erythroid (BFU-E) colonies in methylcellulose from peripheral blood of @entity1 with @entity3458 and extracting the hemoglobin for high-performance liquid chromatography analysis of HbF. @entity1862 and other known RR inhibitors, along with cytotoxic agents that are not RR inhibitors, were tested for the ability to induce HbF using this in vitro assay. RESULTS: @entity1862 decreased the number of BFU-E colonies that grew in culture and significantly increased HbF from 13.6%+/-6.2% to 25.4%+/-8.0% at 50 microM HU (p=0.012). Three other known RR inhibitors also significantly induced HbF: @entity70305 (p=0.025), @entity31571 (p=0.008), and @entity136 (p=0.028). @entity2592 and alkylating agents BCNU and @entity9987 , which are cytotoxic agents but not RR inhibitors, reduced BFU-E colony number but did not significantly induce HbF. CONCLUSION: @entity1862 and other RR inhibitors significantly induce HbF in vitro in @entity1 erythroid progenitor cells. Inhibition of RR may be a critical mechanism by which @entity1862 increases HbF in vivo in @entity1 with @entity3458 .

In vitro induction of fetal hemoglobin in XXXX erythroid progenitor cells.

@entity1 :: ('9606', 'Species') :: ['children', 'human', 'patients'] @entity31571 :: ('MESH:D006144', 'Chemical') :: ['guanazole'] @entity1862 :: ('MESH:D006918', 'Chemical') :: ['Hydroxyurea', 'hydroxyurea'] @entity9987 :: ('MESH:C011272', 'Chemical') :: ['4-hydroperoxycyclophosphamide'] @entity3458 :: ('MESH:D000755', 'Disease') :: ['SCA', 'sickle cell anemia'] @entity2592 :: ('MESH:D003561', 'Chemical') :: ['Cytarabine'] @entity70305 :: ('MESH:C013118', 'Chemical') :: ['4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone'] @entity2142 :: ('MESH:D006461', 'Disease') :: ['hemolysis'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine'] @entity2151 :: ('CHEBI:26561', 'Chemical') :: ['ribonucleotide']
@entity1 :: (9606,Species) :: ['human']
