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Hydroxycarbamide modulates components involved in the regulation of adenosine levels in blood cells from sickle-cell anemia patients

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Abstract

Recent studies have demonstrated the role of adenosine (ADO) in sickle-cell anemia (SCA). ADO is produced by CD39 and CD73 and converted to inosine by adenosine deaminase (ADA). We evaluated the effects of hydroxycarbamide (HU) treatment on the modulation of adenosine levels in SCA patients. The expressions of CD39, CD73, and CD26 were evaluated by flow cytometry on blood cells in 15 HU-treated and 17 untreated patients and 10 healthy individuals. RNA was extracted from monocytes, and ADA gene expression was quantified by real-time PCR. ADA activity was also evaluated. We found that ADA transcripts were two times higher in monocytes of HU-treated patients, compared with untreated (P = 0.039). Monocytes of HU-treated patients expressed CD26, while monocytes of controls and untreated patients did not (P = 0.023). In treated patients, a lower percentage of T lymphocytes expressed CD39 compared with untreated (P = 0.003), and the percentage of T regulatory (Treg) cells was reduced in the treated group compared with untreated (P = 0.017) and controls (P = 0.0009). Besides, HU-treated patients displayed increased ADA activity, compared with untreated. Our results indicate a novel mechanism of action of HU mediated by the reduction of adenosine levels and its effects on pathophysiological processes in SCA.

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Acknowledgments

The authors would like to thank Flávia I. S. Ferreira, Patrícia V. B. Palma, Amélia G. Araujo, Regina H. C. Queiroz, Camila C. B. O. Menezes, and Marli H. Tavella for their assistance with the laboratory techniques and Sandra Navarro Bresciani for assisting in the preparation of the figures.

Funding

This work was supported by the following: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Financiadora de Estudos e Projetos (FINEP), Brazil, and by the INSERM (Institut National de la Santé et de la Recherche Médicale), France.

Author contributions

ACSP designed the study, performed experiments, analyzed and interpreted data, and wrote the manuscript. CDC, FSA, FISF, PVBP, AGA, and RHCQ performed experiments, analyzed and interpreted data, and wrote the manuscript. JE, DTC, MAZ, and RAP designed the study, analyzed and interpreted data, and wrote the manuscript.

Conflict of interest

The authors report no potential conflicts of interest.

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Authors and Affiliations

  1. National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC) and Regional Blood Center, Faculty of Medicine (FMRP), University of São Paulo (USP), Rua Tenente Catão Roxo, 2.501, Bairro Monte Alegre, Campus Universitário, Ribeirão Preto, São Paulo, 14051-140, Brazil

    Ana C. Silva-Pinto, Carolina Dias-Carlos, Patrícia V. B. Palma, Amélia G. Araujo, Dimas T. Covas, Marco A. Zago & Rodrigo A. Panepucci

  2. Department of Pharmacy, Faculty of Health Sciences, University of Brasília (UnB), Brasília, Brazil

    Felipe Saldanha-Araujo

  3. Faculty of Pharmacological Science of Ribeirão Preto, Department of Clinical, Toxicological and Bromatological Analysis, University of São Paulo, Ribeirão Preto, Brazil

    Flávia I. S. Ferreira & Regina H. C. Queiroz

  4. Unité Mixte du Recherch-UMR 763 (INSERM), Hôpital Robert Debré, Université Paris Diderot, Paris, France

    Jacques Elion

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  1. Ana C. Silva-Pinto
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  2. Carolina Dias-Carlos
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  3. Felipe Saldanha-Araujo
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  5. Patrícia V. B. Palma
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  6. Amélia G. Araujo
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  7. Regina H. C. Queiroz
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  8. Jacques Elion
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  9. Dimas T. Covas
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  10. Marco A. Zago
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  11. Rodrigo A. Panepucci
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Correspondence to Ana C. Silva-Pinto.

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Silva-Pinto, A.C., Dias-Carlos, C., Saldanha-Araujo, F. et al. Hydroxycarbamide modulates components involved in the regulation of adenosine levels in blood cells from sickle-cell anemia patients. Ann Hematol 93, 1457–1465 (2014). https://doi.org/10.1007/s00277-014-2066-4

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  • DOI: https://doi.org/10.1007/s00277-014-2066-4

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