title: Relationship of burst-forming-unit-erythroid progenitors and their DNA-synthesis stage to fetal hemoglobin levels in hydroxyurea-treated patients with sickle cell anemia.
abstract: DNA-synthesis stage and total number of circulating burst-forming-units-erythroid (BFU-E) have been inversely correlated with hemoglobin F levels in the peripheral blood, as well as in the cells from the BFU-E-derived colonies obtained from homozygous sickle cell anemia (SS) patients during steady state. Similar studies in SS patients treated with cytotoxic agents have not been reported. However, regeneration of the erythroid marrow that follows the cytoreduction phase of chemotherapy has been suggested as one of the mechanisms of stimulation of fetal hemoglobin synthesis. Therefore, a longitudinal study of hemopoiesis in hydroxyurea-treated SS patients was conducted. Thirty-two sets of hemopoietic studies, including total circulating BFU-E and S-phase BFU-E, were obtained from three patients treated with hydroxyurea. A dose-dependent decrease in total BFU-E colonies occurred in peripheral blood of all three patients (r = -0.58, -0.85, and -0.97, respectively, with each P < 0.05). There was a strong positive correlation between hydroxyurea dose and fetal hemoglobin levels in two of the three patients who responded clinically (r = 0.89618 and 0.88632, respectively, with each P < 0.01). When data from all patients were combined (n = 32), there was a strong, inverse, linear relationship between total number of BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (r = -0.6649 and -0.7404, respectively, with each P < 0.0001). A stronger, curvilinear, multiple relationship was detected between total BFU-E and percentage S-phase BFU-E with fetal hemoglobin levels (R = 0.8351 and 0.8602 with each P < 0.0001).
authors.affiliation: Department of Pediatrics, University of Kentucky, Lexington.
authors.forename: V N
authors.initials: VN
authors.lastname: Mankad
authors.forename: S
authors.initials: S
authors.lastname: Baliga
authors.forename: K
authors.initials: K
authors.lastname: Phillips
authors.forename: A K
authors.initials: AK
authors.lastname: Shah
authors.forename: Y M
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D016196:S Phase
chemical_list: D004247:DNA; D005319:Fetal Hemoglobin; D006918:Hydroxyurea