International Journal of Hematology

DOI: 10.1007/s12185-016-2173-1 Pages: 614-622

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

1. Kitasato University School of Medicine, Department of Pathology

2. Kitasato University School of Medicine, Department of Hematology

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

Correspondence to:
Yoshiki Murakumo
Tel: +81-42-778-9020
Email: murakumo@med.kitasato-u.ac.jp

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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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