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  • Title: Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease.
    Author: Odièvre MH, Bony V, Benkerrou M, Lapouméroulie C, Alberti C, Ducrocq R, Jacqz-Aigrain E, Elion J, Cartron JP.
    Journal: Haematologica; 2008 Apr; 93(4):502-10. PubMed ID: 18322255.
    Abstract:
    BACKGROUND: We investigated adhesion receptor levels on red blood cells, reticulocytes and erythroid progenitors from children with sickle cell disease treated or not with hydroxyurea. DESIGN AND METHODS: Four groups of patients were investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events (n=26); (ii) untreated children with a history of vaso-occlusive events (n=20); (iii) children with no history of vaso-occlusive events (n=28); and (iv) healthy African controls (n=27). Expression of adhesion receptors was analyzed by flow cytometry with specific mono-clonal antibodies. RESULTS: Reticulocytes and/or red blood cells from the children with sickle cell disease showed significantly higher expression of CD36, alpha 4beta 1, Lu/BCAM than those from controls, whatever the severity of the disease, as well as less marked increases in expression of ICAM-4, CD47 and CD147. Under hydroxyurea treatment, the expression of CD36, alpha 4beta 1 and ICAM-4 (to a lesser extent) was decreased, but surprisingly the expression of Lu/BCAM (and also CD47 and CD147 to a lesser extent) was significantly increased. Alterations of levels of adhesion receptors could be recapitulated in two-phase liquid cultures of erythroid progenitors from controls and untreated children with a history of vaso-occlusive disease, grown in the absence or presence of hydroxyurea. CONCLUSIONS: Our results suggest that hydroxyurea acts during erythroid development and modulates adhesion receptor expression and function differently, possibly by acting on gene expression and the signaling cascade leading to receptor activation.
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