Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model

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Published Ahead of Print on April 7, 2010, as doi:10.3324/haematol.2010.023325. Copyright 2010 Ferrata Storti Foundation.

Haematologica 2010 [Epub ahead of print] Citation: Lebensburger J, Pestina T, Ware R, Boyd K, and Persons D.

1 Published Ahead of Print on April 7, 2010, as doi: /haematol Copyright 2010 Ferrata Storti Foundation. Early Release Paper Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model by Jeffrey Lebensburger, Tamara Pestina, Russell Ware, Kelli Boyd, and Derek Persons Haematologica 2010 [Epub ahead of print] Citation: Lebensburger J, Pestina T, Ware R, Boyd K, and Persons D. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model. Haematologica. 2010; 96:xxx doi: /haematol Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process. Haematologica (pissn: , eissn: , NLM ID: , publishes peer-reviewed papers across all areas of experimental and clinical hematology. The journal is owned by the Ferrata Storti Foundation, a non-profit organization, and serves the scientific community with strict adherence to the principles of open access publishing ( In addition, the journal makes every paper published immediately available in PubMed Central (PMC), the US National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature. Support Haematologica and Open Access Publishing by becoming a member of the European Hematology Association (EHA) and enjoying the benefits of this membership, which include free participation in the online CME program Official Organ of the European Hematology Association Published by the Ferrata Storti Foundation, Pavia, Italy

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26 1. Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore) Nov;84(6): Herman EC, Jr., Conley CL. Hereditary persistence of fetal hemoglobin. A family study. Am J Med Jul;29: Pembrey ME, Wood WG, Weatherall DJ, Perrine RP. Fetal haemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia. Br J Haematol Nov;40(3): DeSimone J, Heller P, Hall L, Zwiers D. 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc Natl Acad Sci U S A Jul;79(14): Dover GJ, Humphries RK, Moore JG, Ley TJ, Young NS, Charache S, et al. Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. Blood Mar;67(3): Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med May 18;332(20): Hankins JS, Helton KJ, McCarville MB, Li CS, Wang WC, Ware RE. Preservation of spleen and brain function in children with sickle cell anemia treated with hydroxyurea. Pediatr Blood Cancer Feb;50(2): Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, et al. Pain in sickle cell disease. Rates and risk factors. N Engl J Med Jul 4;325(1): Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med Jun 9;330(23): Powars DR, Weiss JN, Chan LS, Schroeder WA. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia? Blood Apr;63(4): Bookchin RM, Nagel RL. Interactions between human hemoglobins: sickling and related phenomena. Semin Hematol Oct;11(4): Charache S, Barton FB, Moore RD, Terrin ML, Steinberg MH, Dover GJ, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) Nov;75(6): Zimmerman SA, Schultz WH, Davis JS, Pickens CV, Mortier NA, Howard TA, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood Mar 15;103(6): Covas DT, de Lucena Angulo I, Vianna Bonini Palma P, Zago MA. Effects of hydroxyurea on the membrane of erythrocytes and platelets in sickle cell anemia. Haematologica Mar;89(3): Styles LA, Lubin B, Vichinsky E, Lawrence S, Hua M, Test S, et al. Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood Apr 1;89(7): Hillery CA, Du MC, Wang WC, Scott JP. Hydroxyurea therapy decreases the in vitro adhesion of sickle erythrocytes to thrombospondin and laminin. Br J Haematol May;109(2):

27 17. Cokic VP, Beleslin-Cokic BB, Tomic M, Stojilkovic SS, Noguchi CT, Schechter AN. Hydroxyurea induces the enos-cgmp pathway in endothelial cells. Blood Jul 1;108(1): Bridges KR, Barabino GD, Brugnara C, Cho MR, Christoph GW, Dover G, et al. A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. Blood Dec 15;88(12): Paszty C, Brion CM, Manci E, Witkowska HE, Stevens ME, Mohandas N, et al. Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science Oct 31;278(5339): Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm. Proc Natl Acad Sci U S A Mar 5;99(5): Belcher JD, Bryant CJ, Nguyen J, Bowlin PR, Kielbik MC, Bischof JC, et al. Transgenic sickle mice have vascular inflammation. Blood May 15;101(10): Kaul DK, Liu XD, Fabry ME, Nagel RL. Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol Jun;278(6):H Pestina TI, Hargrove PW, Jay D, Gray JT, Boyd KM, Persons DA. Correction of murine sickle cell disease using gamma-globin lentiviral vectors to mediate high-level expression of fetal hemoglobin. Mol Ther Feb;17(2): Manci EA, Hillery CA, Bodian CA, Zhang ZG, Lutty GA, Coller BS. Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease. Blood Feb 15;107(4):

HU: Myths and Facts. Melanie Kirby Associate Professor of Paediatrics

HU: Myths and Facts. Melanie Kirby Associate Professor of Paediatrics HU: Myths and Facts Melanie Kirby Associate Professor of Paediatrics SACGO Hamilton, Ontario March 5, 2016 Declaration of Disclosure I have no actual or potential conflict of interest in relation to this