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CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma

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Abstract

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that negatively regulates TGF-β signaling. CD109 was originally identified in hematopoietic tumors; however, the significance of CD109 in hematopoietic malignancies remains unclear. Here, we study the association of CD109 with diffuse large B-cell lymphoma (DLBCL) prognosis. Eighty-four DLBCL specimens were immunohistochemically analyzed for CD109 expression, and 31 and 53 cases were classified into low- and high-CD109 expression groups, respectively. CD109 expression was not associated with overall survival using the Kaplan–Meier analysis and log-rank tests (P = 0.17); however, a significant association was observed between high-CD109 expression and low-1-year survival (P = 0.01). Moreover, in combination with the revised International Prognostic Index (R-IPI), R-IPI-poor/CD109-high was associated with poorer prognosis compared with R-IPI-poor alone. We assessed TGF-β signaling in CD109-depleted Nalm6 cells (a human B-lymphoblastic leukemia/lymphoma cell line), and found prolonged Smad2 phosphorylation compared with control cells after TGF-β1 stimulation, suggesting that CD109 attenuates TGF-β1 signaling in human B-cell tumors. These results suggest that CD109 is a putative biomarker for identifying a high-risk group among DLBCL patients.

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Acknowledgements

This work was supported by Keyaki-kai Grant from the Graduate School of Medical Science, Kitasato University.

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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

    Maki Yokoyama, Masaaki Ichinoe, Sosei Okina, Yasutaka Sakurai, Norihiro Nakada, Nobuyuki Yanagisawa, Shi-Xu Jiang, Yoshiko Numata, Atsuko Umezawa & Yoshiki Murakumo

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

    Maki Yokoyama, Sosei Okina & Masaaki Higashihara

  3. Department of Transfusion and Cell Transplantation, Kitasato University School of Medicine, Sagamihara, Japan

    Koji Miyazaki

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  1. Maki Yokoyama
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Correspondence to Yoshiki Murakumo.

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Yokoyama, M., Ichinoe, M., Okina, S. et al. CD109, a negative regulator of TGF-β signaling, is a putative risk marker in diffuse large B-cell lymphoma. Int J Hematol 105, 614–622 (2017). https://doi.org/10.1007/s12185-016-2173-1

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  • DOI: https://doi.org/10.1007/s12185-016-2173-1

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