HbF that modulate sickle hemoglobin polymerization may help in the design of novel therapies for HU-resistant SCA patients
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چکیده
correlated positively and negatively with the percentage of normal and abnormal cells, respectively (Figure 1B-C). Fluorescent labeling of HbF allowed us to discriminate nonF-cells (Figure 1Di-ii) fromF-cells (Figure 1Diii-iv), and analyze their shape as captured in the brightfield images. The images confirmed the prediction that some RBCs with detectable HbF content still sickle (Figure 1Div), and also identified RBCs that are resistant to sickling despite no detectable HbF (Figure 1Dii). The percentage of non-Fcells sickling on deoxygenation was significantly higher than among F-cells (20.08% [95% CI 15.56-24.60] vs 13.44% [95% CI 10.2116.68], P, .0001). This difference was statistically significant both in patients not taking HU and in treated patients (Figure 1F). F-cells from patients on HU sickled significantly less than F-cells from patients off HU, and the same difference was borderline significant when comparing non-F-cells from patients onHUwith those off HU. Our observations support that the threshold used for detection of F-cells is not the same threshold that defines protection against sickling. Similar to previous investigators, we also have found that the very high concentration of intraerythrocytic hemoglobin poses a difficult challenge in achieving the antigen saturation with antig-globin antibody that is necessary to measure accurately the amount of HbF per F-cell, which will be needed ultimately to test fully the mathematical modeling predictions of Steinberg et al. Differential RBCsusceptibility of non-F-cells to sicklingbetweenpatientsonor off HU also supports the existence of additional beneficial mechanisms of HU other than HbF induction. The identification of factors besides HbF that modulate sickle hemoglobin polymerization may help in the design of novel therapies for HU-resistant SCA patients.
منابع مشابه
Side effects of hydroxyurea in patients with Thalassemia major and thalassemia intermedia and sickle cell anemia
Background Sickle hemoglobin is the most common abnormal hemoglobin in the United States. Hemoglobin S arises as a result of a single amino acid substitution (glutamic acid to valin at position 6 of the β-globine chain). The presence of fetal hemoglobin (HbF) plays a relatively protective role since a significant amount of HbF interferes with HbS polymerization, the pathogenesis mechanism of ...
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Hydroxyurea (HU) enhances the production of fetal hemoglobin (HbF) and on the other hand this event can decreases the frequency of painful crises in sickle cell anemia (SCA). We studied the efficiency of HU in reducing painful crises and it’s effect on HbF production rate and on other hematologic values in 40 SCA patients. Median age of patients was 20 years. Eighteen were male and 22 were fe...
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Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-geno...
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