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TMEM4 is Highly Expressed in Plasma Cell Neoplasms and Associated with B Lymphocyte Differentiation

Chen-Feng Qi, Shao Xiang, Guifang Ouyang, Xing-pei Hao, Min Sun Shin, Alexander L Kovalchuk, Peng Liang, Huabao Xiong, Herbert C Morse III, Zhengping Zhuang, Jeff X Zhou and Susan K Pierce

Aiming to identifybiomarkers for plasma cell neoplasms, we analyzed gene expression profile and proteomic characteristics of mouse models of plasmacytomas along with other types of B-cell neoplasms. We found that transmembrane protein 4 (Tmem4) was highly expressed in plasmacytomas in comparison with early-stage B-cell neoplasms. The serum levels of Tmem4 were also significantly greater in mice with plasmacytoma comparing to those with early-stage B-cell neoplasms (P<0.01). Mechanistically, increased Tmem4 expression in B cells led to increased levels of IL-10, a cytokine that promotes the growth of malignant plasma cells and participates in the terminal differentiation of B cells into plasma cells. In addition, over-expression of Tmem4 promoted B cell terminal differentiation as evidenced by the increase in expression of XBP1, CD38, and CD138. Furthermore, we found that TMEM4 was highly expressed in plasma cells of multiple myeloma patients. These findings suggested that Tmem4 plays an important role in plasma cell differentiation and has a potential to serve as a biomarker for plasma cell neoplasms.