Kiyoko Kawamura1, Akihiko Wada1,2, Ji-Yang Wang3,4, Quanhai Li1,5, Akihiro Ishii6, Hideki Tsujimura6, Toshiyuki Takagi6, Makiko Itami7, Yuji Tada2, Koichiro Tatsumi2, Hideaki Shimada8, Kenzo Hiroshima9, Masatoshi Tagawa10,11. 1. Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. 2. Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. 3. Department of Immunology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai, 200032, China. 4. Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. 5. Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. 6. Division of Hematology-Oncology, Chiba Cancer Center, 66-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. 7. Division of Surgical Pathology, Chiba Cancer Center, 66-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. 8. Department of Surgery, School of Medicine, Toho University, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan. 9. Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owadasinden, Yachiyo, 276-8524, Japan. 10. Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba, 260-8717, Japan. mtagawa@chiba-cc.jp. 11. Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. mtagawa@chiba-cc.jp.
Abstract
PURPOSE: Activation-induced cytidine deaminase (AID) is involved in somatic hypermutation and class switch recombination processes in the antibody formation. The AID activity induces gene mutations and could be associated with transformation processes of B cells. Nevertheless, the relation between AID expression and the prognosis of B cell lymphoma patients remains uncharacterized. METHODS: We examined expression levels of the AID gene in 89 lymph node specimens from lymphoma and non-lymphoma patients with Northern blot analysis and investigated an association with their survival. RESULTS: The AID gene was preferentially expressed in B cell lymphoma in particular in diffuse large B cell lymphoma and follicular lymphoma. We confirmed AID protein expression in the mRNA-positive but not in the negative specimens with Western blot analysis and immunohistochemical staining. Survival of the patients treated with cyclophosphamide-/doxorubicin-/vincristine-/prednisone-based chemotherapy demonstrated that the prognosis of diffuse large B cell patients was unfavorable in the mRNA-positive group compared with the negative group, and that AID expression levels were correlated with the poor prognosis. In contrast, AID expression was not linked with the prognosis of follicular lymphoma patients. CONCLUSIONS: AID expression is a predictive marker for an unfavorable outcome in DLBCL patients treated with the chemotherapy.
PURPOSE:Activation-induced cytidine deaminase (AID) is involved in somatic hypermutation and class switch recombination processes in the antibody formation. The AID activity induces gene mutations and could be associated with transformation processes of B cells. Nevertheless, the relation between AID expression and the prognosis of B cell lymphomapatients remains uncharacterized. METHODS: We examined expression levels of the AID gene in 89 lymph node specimens from lymphoma and non-lymphomapatients with Northern blot analysis and investigated an association with their survival. RESULTS: The AID gene was preferentially expressed in B cell lymphoma in particular in diffuse large B cell lymphoma and follicular lymphoma. We confirmed AID protein expression in the mRNA-positive but not in the negative specimens with Western blot analysis and immunohistochemical staining. Survival of the patients treated with cyclophosphamide-/doxorubicin-/vincristine-/prednisone-based chemotherapy demonstrated that the prognosis of diffuse large B cell patients was unfavorable in the mRNA-positive group compared with the negative group, and that AID expression levels were correlated with the poor prognosis. In contrast, AID expression was not linked with the prognosis of follicular lymphomapatients. CONCLUSIONS:AID expression is a predictive marker for an unfavorable outcome in DLBCL patients treated with the chemotherapy.
Entities:
Keywords:
Activation-induced cytidine deaminase; Diffuse large B cell lymphoma; Prognosis
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