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High expression of REV7 is an independent prognostic indicator in patients with diffuse large B-cell lymphoma treated with rituximab

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Abstract

REV7 is a multifunctional protein involved in DNA damage tolerance, cell-cycle regulation, gene expression, and carcinogenesis. Although its expression is reportedly associated with poor prognosis in human solid tissue cancers, the significance of REV7 expression in hematopoietic malignancies is unclear. This study evaluated the prognostic significance of REV7 expression in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-combined chemotherapy. Using immunohistochemistry, we analyzed 83 specimens of de novo DLBCL [38 germinal center B-cell-like (GCB) and 45 non-GCB DLBCLs] treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone for REV7 expression. Aberrant REV7 expression was detected in DLBCL cell nuclei. High REV7 expression was associated with significantly shorter overall survival (OS) and progression-free survival (PFS) using Kaplan–Meier analysis and log-rank tests (P < 0.01 and P < 0.01, respectively). Multivariate analysis revealed that REV7 expression is an independent prognostic factor for both OS and PFS. Additionally, when patients were divided into four groups using a combination of REV7 expression and international prognostic index (IPI) or Bcl-2 expression, REV7High/IPIPoor and REV7High/Bcl-2High patients showed the poorest outcome. These results indicate that REV7 may be a useful biomarker to predict the prognosis of patients with DLBCL treated with rituximab.

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research (C) commissioned by the Ministry of Education, Culture, Sports, Science and Technology of Japan (to YM, 24590479).

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Authors and Affiliations

  1. Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Sosei Okina, Nobuyuki Yanagisawa, Maki Yokoyama, Yasutaka Sakurai, Yoshiko Numata, Atsuko Umezawa & Yoshiki Murakumo

  2. Department of Hematology, Kitasato University School of Medicine, Sagamihara, Japan

    Sosei Okina, Maki Yokoyama & Masaaki Higashihara

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  1. Sosei Okina
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  2. Nobuyuki Yanagisawa
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  3. Maki Yokoyama
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  4. Yasutaka Sakurai
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Correspondence to Yoshiki Murakumo.

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Okina, S., Yanagisawa, N., Yokoyama, M. et al. High expression of REV7 is an independent prognostic indicator in patients with diffuse large B-cell lymphoma treated with rituximab. Int J Hematol 102, 662–669 (2015). https://doi.org/10.1007/s12185-015-1880-3

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