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Expression of peroxiredoxins I and IV in multiple myeloma: association with immunoglobulin accumulation

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Abstract

B cell malignancies are classified according to the postulated differentiation stage of the originating cell. During differentiation, structural and molecular changes occur to support massive processing of immunoglobulin in the endoplasmic reticulum (ER) of plasma cells at the final stage. When overloaded, the ER generates unfolded proteins and hydrogen peroxide (H2O2), which may cause cell death. Peroxiredoxins (Prxs) I and IV belong to a family of proteins able to catalyze peroxide detoxification. Here, we investigated a potential association of these enzymes with immunoglobulin production in B cell neoplasms. Our results demonstrated that the expression of Prx IV was induced as cells became competent to synthesize immunoglobulin light chains, as observed by immunohistochemistry in tissue sections of B cell neoplasms and also by qPCR and Western blotting analyses in malignant B cell lines. Prx I was frequently highly expressed, indicating additional regulatory processes besides ER activity. Results obtained exclusively with myeloma cells have shown that expression of Prxs I and IV, both at mRNA and protein levels, was associated with light chain secretion quantified by ELISA. We suggest that Prxs I and IV may provide survival advantages for terminally differentiated neoplastic B cells by the elimination of H2O2 and, in the case of Prx IV, by the conversion of this toxic in a functional agent driving oxidative protein folding in the ER. In this sense, multiple myeloma and lymphomas demonstrated to synthesize immunoglobulin chains may benefit from strategic therapies targeting the adaptive pathway to ER stress, including inhibition of Prxs I and IV activity.

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Acknowledgments

This work was supported by the Brazilian Agency FAPESP. We thank Jeruza Pinheiro da Silveira Bossonaro, Pollyanna Montaldi, Francesca Ramos da Silva, and Bruno Lima Rodrigues for their excellent technical assistance.

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Authors and Affiliations

  1. Faculty of Dentistry, Department of Pathology, São Leopoldo Mandic Institute and Research Center, Rua José Rocha Junqueira, 13, 13045-755, Campinas, São Paulo, Brazil

    Ana Paula Dias Demasi, Elizabeth Ferreira Martinez, Marcelo Henrique Napimoga, Andresa Borges Soares, Ney Soares Araujo & Vera Cavalcanti Araujo

  2. Department of Pathology, School of Medicine, State University of Campinas, Campinas, Brazil

    Leandro Lopes Freitas

  3. Laboratory of Investigative and Molecular Pathology, CIPED, State University of Campinas, Campinas, Brazil

    Jose Vassallo

  4. Hematology and Hemotherapy Center, School of Medicine, State University of Campinas, Campinas, Brazil

    Adriana Silva Santos Duarte

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  1. Ana Paula Dias Demasi
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  2. Elizabeth Ferreira Martinez
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  3. Marcelo Henrique Napimoga
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  9. Vera Cavalcanti Araujo
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Correspondence to Ana Paula Dias Demasi.

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Demasi, A.P.D., Martinez, E.F., Napimoga, M.H. et al. Expression of peroxiredoxins I and IV in multiple myeloma: association with immunoglobulin accumulation. Virchows Arch 463, 47–55 (2013). https://doi.org/10.1007/s00428-013-1433-1

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  • DOI: https://doi.org/10.1007/s00428-013-1433-1

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