Journal
INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 105, Issue 5, Pages 614-622Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s12185-016-2173-1
Keywords
CD109; Diffuse large B-cell lymphoma; Prognosis; TGF-beta signaling
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Funding
- Keyaki-kai Grant from the Graduate School of Medical Science, Kitasato University
- Grants-in-Aid for Scientific Research [15H02822] Funding Source: KAKEN
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CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that negatively regulates TGF-beta 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-beta 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-beta 1 stimulation, suggesting that CD109 attenuates TGF-beta 1 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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