EBV関連リンパ増殖異常症の新分類画定を目指した臨床病理学的、生物学的研究

• 研究課題/領域番号: 19590344
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 人体病理学
• 研究機関: 名古屋大学
• 研究代表者: 中村 栄男 名古屋大学, 大学院・医学系・研究科, 教授 (80180363)
• 研究期間 (年度): 2007 – 2008
• 研究課題ステータス: 完了 (2008年度)
• 配分額: 4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円); 2008年度: 780千円 (直接経費: 600千円、間接経費: 180千円); 2007年度: 3,900千円 (直接経費: 3,000千円、間接経費: 900千円)
• キーワード: 病理 / 癌 / 加齢 / 病理学 / 免疫機能異常 / EBV / 悪性リンパ腫

研究概要

加齢性EBV関連B細胞リンパ増殖異常症は、本邦より我々が世界に初めて発信した疾患概念である。世界に類例なき高齢化に向かいつつある本邦において、初めて認識が可能であった疾患である。2008年9月に公刊されたWHO分類第4版に正式な項目として掲載された。本疾患の正式掲載以降、欧米でも同様の疾患の報告とともに、加齢に伴う免疫機能の低下の関与とその臨床病理学的重要性が急速に指摘されつつある。当該期間において、これらEBV関連リンパ増殖症の免疫監視機構の解明を含む体系的理解、新分類の画定、さらに新たな治療法、予防法の開発を目指して研究を遂行した。

研究成果

• [雑誌論文] Array comparative genomic hybridization analysis of PTCL-U reveals a distinct subgroup with genetic alterations similar to lymphoma-type adult T-cell leukemia/lymphoina. (2009)
  • 著者名/発表者名: Nakagawa M, et al.
  • 雑誌名: Clin Cancer Res. 15 ページ: 30-38
  • 査読あり
• [雑誌論文] Age-related EBV-associated B-cell lymphoproliferative disorders: comparison with EBV-positive classical Hodgkin lymphoma in elderly patients (2008)
  • 著者名/発表者名: Asano N, Yamamoto K, Tamaru JI, Oyama T, Ishida F, Ohshima K, Yoshino T, Nakamura N, Mori S, Yoshie O, Shimoyama Y, Morishima Y, Kinoshita T, Nakamura S.
  • 雑誌名: Blood
  • NAID: 40019064261
  • 査読あり
• [雑誌論文] Clinical differences between nasal and extranasal NK/T cell lymphoma: a study of 136 cases from the International Peripheral T cell Lymphoma Project (2008)
  • 著者名/発表者名: Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, Vose J, Armitage JO, Liang R.
  • 雑誌名: Blood 48(2) ページ: 39-45
  • 査読あり
• [雑誌論文] Post-transplant plasmacytoma without Epstein-Barr virus infection occurring rapidly after unrelated allogeneic bone marrow transplantation (2008)
  • 著者名/発表者名: Kawakami K, Miyanishi S, Nakano Y, Mitani H, Nakao M, Murata T, Baba Y, Nakamura S.
  • 雑誌名: Int J Hematol
  • NAID: 10023971539
  • 査読あり
• [雑誌論文] "Follicular Variant" of Hyaline-vascular Type of Castleman's Disease : Histopathological and Immunohistochemical Study of 11 Cases (2008)
  • 著者名/発表者名: Kojima M, Shimizu K, Ikota H, Ohno Y, Motoori T, Itoh H, Masawa N, Nakamura S.
  • 雑誌名: J Clin Exp Hematop 48(2) ページ: 39-45
  • NAID: 10023917233
  • 査読あり
• [雑誌論文] Japanese phase II study of (90)Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma (2008)
  • 著者名/発表者名: Tobinai K, Watanabe T, Ogura M, Morishima Y, Hotta T, Ishizawa K, Itoh K, Okamoto SI, Taniwaki M, Tsukamoto N, Okumura H, Terauchi T, Nawano S, Matsusako M, Matsuno Y, Nakamura S, Mori S, Ohashi Y, Hayashi M, Endo K.
  • 雑誌名: Cancer Sci.
  • NAID: 10025141786
  • 査読あり
• [雑誌論文] Cytogenetic abnormality 46,XX,add(21)(q11.2) in a patient with follicular dendritic cell sarcoma (2008)
  • 著者名/発表者名: Suzuki N, Katsusihma H, Takeuchi K, Nakamura S, Ishizawa K, Ishii S, Moriya T, DeCoteau JF, Miura I, Ichinohasama R.
  • 雑誌名: Cancer Genet Cytogenet 186(1) ページ: 54-7
  • 査読あり
• [雑誌論文] De novo CD5+ diffuse large B-cell lymphoma : results of a detailed clinicopathological review in 120 patients (2008)
  • 著者名/発表者名: Yamaguchi M, Nakamura N, Suzuki R, KagamiY, Okamoto M, Ichinohasama R, Yoshino T, Suzumiya J, Murase T, Miura I, Ohshima K, Nishikori M, Tamaru JI, Taniwaki M, Hirano M, Morishima Y, Ueda R, Shiku H, Nakamura S.
  • 雑誌名: Haematologica 93(8) ページ: 1195-202
  • 査読あり
• [雑誌論文] Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan (2008)
  • 著者名/発表者名: Shimada K, Matsue K, Yamamoto K, Murase T, Ichikawa N, Okamoto M, Niitsu N, Kosugi H, Tsukamoto N, Miwa H, Asaoku H, Kikuchi A, Matsumoto M, Saburi Y, Masaki Y, Yamaguchi M, Nakamura S, Naoe T, Kinoshita T.
  • 雑誌名: J Clin Oncol 26(19) ページ: 3189-92
  • 査読あり
• [雑誌論文] Nodal T/NK-cell lymphoma of nasal type : a clinicopathological study of six cases (2008)
  • 著者名/発表者名: Takahashi E, Asano N, Li C, Tanaka T, Shimada K, Shimada S, Yoshino T, Kojima M, Hara K, Eimoto T, Nakamura S.
  • 雑誌名: Histopathology 52(5) ページ: 585-96
  • 査読あり
• [雑誌論文] Age-related EBV-associated B-cell lymphoproliferative disorders : comparison with EBV-positive classical Hodgkin lymphoma in elderly patients. (2008)
  • 著者名/発表者名: Asano N, et al.
  • 雑誌名: Blood. (Epub ahead of print)
  • 査読あり
• [雑誌論文] Abnormal cytoplasmic dyslocalisation and/or reduction of nucleop hosmin protein level rarely occurs in myelodysplastic syndromes. (2008)
  • 著者名/発表者名: Ishikawa Y, et al.
  • 雑誌名: Leuk Lymphoma. 49 ページ: 2359-2364
  • 査読あり
• [雑誌論文] Histological assessment of bile lake formation after hepatic porto enterostomy for biliary atresia. (2008)
  • 著者名/発表者名: Taninaka T, et al.
  • 雑誌名: Pediatr Surg Int. 24 ページ: 265-269
  • 査読あり
• [雑誌論文] Clinical differences between nasal and extranasal NK/T-cell lymp homa : a study of 136 cases from the International Peripheral T-cell Lymphoma Project. (2008)
  • 著者名/発表者名: Au WY, et al.
  • 雑誌名: Blood. (Epub ahead of print)
  • 査読あり
• [雑誌論文] Post-transplant plasmacytoma without Epstein-Barr virus infection occurring rapidly after unrelated allogeneic bone marrow trans plantation. (2008)
  • 著者名/発表者名: Kawakami K, et al.
  • 雑誌名: Int J Hematol. 88 ページ: 606-609
  • 査読あり
• [雑誌論文] "FoUicular Variant" of Hyaline-vascular Type of Castleman's Disease : Histopathological and Immunohistochemical study of 11 Cases. (2008)
  • 著者名/発表者名: Kojima M, et al.
  • 雑誌名: Clin Exp Hematop. 48 ページ: 39-45
  • 査読あり
• [雑誌論文] Japanese phase II study of (90) Y-ibritumoinab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma. (2008)
  • 著者名/発表者名: Tobinai K, et al.
  • 雑誌名: Cancer Sci. (Epub ahead of print)
  • 査読あり
• [雑誌論文] Cytogenetic abnormality 46, XX, add(21)(q11.2) in a patient with follicular dendritic cell sarcoma. (2008)
  • 著者名/発表者名: Suzuki N, et al.
  • 雑誌名: Cancer Genet Cytogenet. 186 ページ: 54-57
  • 査読あり
• [雑誌論文] Significance of CXCR3 expression in gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type for predicting responsiveness to Helicobacter pylori eradication. (2008)
  • 著者名/発表者名: Yamamoto H, et al.
  • 雑誌名: Cancer Sci. 99 ページ: 1769-1773
  • 査読あり
• [雑誌論文] Primary cutaneous T-cell lymphoma of unspecified type with cytotoxic phenotype : Clinicopathological analysis of 27 patients. (2008)
  • 著者名/発表者名: Hagiwara M, et al.
  • 雑誌名: Cancer Sci. (Epub ahead of print)
  • 査読あり
• [雑誌論文] Histological characteristics of 21 Papua New Guinean children with high-grade B-cell lymphoma, which is frequently associated with EBV infectio. (2008)
  • 著者名/発表者名: Nomura Y, et al.
  • 雑誌名: Pathol Int. 58 ページ: 695-700
  • 査読あり
• [雑誌論文] Estimation of the relationship between caspase-3 expression and clinical outcome of Burkitt's and Burkitt-like lymphoma. (2008)
  • 著者名/発表者名: Nomura Y, et al.
  • 雑誌名: Cancer Sci. 99 ページ: 1564-1569
  • 査読あり
• [雑誌論文] Characterization of de novo diffuse large B-cell lymphoma with a translocation of c-myc and immunoglobulin genes. (2008)
  • 著者名/発表者名: Kikuchi A, et al.
  • 雑誌名: Leuk Res. 32 ページ: 1176-1182
  • 査読あり
• [雑誌論文] A case of primary Epstein-Barr virus-associated cutaneous diffuse large B-cell lymphoma unassociated with iatrogenic or endogenous immune dysregulation. (2008)
  • 著者名/発表者名: Tokuda Y, et al.
  • 雑誌名: J Cutan Pathol. 35 ページ: 666-671
  • 査読あり
• [雑誌論文] Lymphoplasmacytic Infiltrate of Regional Lymph Nodes in Kuttner's Tumor (Chronic Sclerosing Sialadenitis) : A Report of 3 Cases. (2008)
  • 著者名/発表者名: Kojima M, et al.
  • 雑誌名: Int J Surg Pathol. 16 ページ: 263-268
  • 査読あり
• [雑誌論文] De novo CD5+ diffuse large B-cell lymphoma : results of a detailed clinicopathological review in 120 patients. (2008)
  • 著者名/発表者名: Yamaguchi M, et al.
  • 雑誌名: Haematologica 93 ページ: 1195-1202
  • 査読あり
• [雑誌論文] Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders : special references to lymphomas surrounding this newly recognized clinicopathologic disease. (2008)
  • 著者名/発表者名: Shimoyama Y, et al.
  • 雑誌名: Cancer Sci 99 ページ: 1085-1091
  • 査読あり
• [雑誌論文] One-step multiplex real-time PCR assay to analyze the latency patterns of Epstein-Barr virus infection. (2008)
  • 著者名/発表者名: Kubota N, et al.
  • 雑誌名: J Virol Methods. 147 ページ: 26-36
  • 査読あり
• [雑誌論文] Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan. (2008)
  • 著者名/発表者名: Shimada K, et al.
  • 雑誌名: J Clin Oncol 26 ページ: 3189-3195
  • 査読あり
• [雑誌論文] Histological diversity of reactive and atypical proliferative lymph node lesions in systemic lupus erythematosus patients. (2008)
  • 著者名/発表者名: Kojima M, et al.
  • 雑誌名: Pathol Res Pract. 203 ページ: 423-431
  • 査読あり
• [雑誌論文] Evaluation of organ involvement in intravascular large B-cell lymphoma by (18) F-nuorodeoxyglucose positron emission tomography. (2008)
  • 著者名/発表者名: Shimada K, et al.
  • 雑誌名: Int J Hematol. 88 ページ: 149-153
  • 査読あり
• [雑誌論文] Characterization of myelodysplastic syndrome and aplastic anemia by immunostaining of p53 and hemoglobin F and karyotype analysis : differential diagnosis between refractory anemia and aplastic anemia. (2008)
  • 著者名/発表者名: Iwasaki T, et al.
  • 雑誌名: Pathol Int. 58 ページ: 353-360
  • 査読あり
• [雑誌論文] Peripheral T-cell lymphoma following diffuse large B-cell lymphoma associated with celiac disease. (2008)
  • 著者名/発表者名: Makishima H, et al.
  • 雑誌名: Intern Med. 47 ページ: 295-298
  • 査読あり
• [雑誌論文] Marginal Zone B-Cell Lymphoma Among Primary B-Cell Lymphoma of Waldeyer's Ring : Histopathologic and Immunohistochemical Study of 16 Tonsillectomy Specimens. (2008)
  • 著者名/発表者名: Kojima M, et al.
  • 雑誌名: Int J Surg Pathol. 16 ページ: 164-170
  • 査読あり
• [雑誌論文] Peripheral T-cell lymphoma resembling Kimura's disease. (2008)
  • 著者名/発表者名: Kojima M, et al.
  • 雑誌名: APMIS. 116 ページ: 212-214
  • 査読あり
• [雑誌論文] Nodal T/NK-cell lymphoma of nasal type : a clinicopathological study of six cases. (2008)
  • 著者名/発表者名: Takahashi E, et al.
  • 雑誌名: Histopathology. 52 ページ: 585-596
  • 査読あり
• [雑誌論文] Extranodal NK/T-cell lymphoma: diagnosis and treatment cues. (2008)
  • 著者名/発表者名: Suzuki R, et. al.
  • 雑誌名: Hematol Oncol. [Epub ahead of print]
  • 査読あり
• [雑誌論文] Expression of CCL17 and CCL22 by latent membrane protein 1-positive tumor cells in age-related EBV-associated B-cell lymphoproliferative disorder. (2008)
  • 著者名/発表者名: Takegawa S, et. al.
  • 雑誌名: Cancer Sci. 99 ページ: 296-302
  • 査読あり
• [雑誌論文] High-grade mature B-cell lymphoma with Burkitt-like morphology: results of a clinicopathological study of 72 Japanese patients. (2008)
  • 著者名/発表者名: Nomura Y, et. al.
  • 雑誌名: Cancer Sci. 99 ページ: 246-252
  • 査読あり
• [雑誌論文] Clinical significance of nuclear non-phosphorylated beta-catenin in acutemyeloid leukaemia and myelodysplastic syndrome. (2008)
  • 著者名/発表者名: Xu J, et. al.
  • 雑誌名: Br J Haematol. 140 ページ: 394-401
  • 査読あり
• [雑誌論文] Carbon beam therapy in recurrent ovarian cancer. (2008)
  • 著者名/発表者名: Nawa A, et. al.
  • 雑誌名: Ann Oncol. 19 ページ: 192-194
  • 査読あり
• [雑誌論文] Plasmacytic hyperplasia in age-related Epstein-Barr virus-associated lymphoproliferative disorders: A report of two cases. (2008)
  • 著者名/発表者名: Kojima M, et. al.
  • 雑誌名: Pathol Res Pract. [Epub ahead of print]
  • 査読あり
• [雑誌論文] Clinical Features and Prognosis of Gastric MALT Lymphoma With Special Reference to Responsiveness to H. pylori Eradication and API2-MALT1 Status. (2008)
  • 著者名/発表者名: Nakamura T, et. al.
  • 雑誌名: Am J Gastroenterol. 103 ページ: 62-70
  • 査読あり
• [雑誌論文] Pulmonary lesion of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia appears to be a cause of lymphoplasmacytic proliferation of the lung: A report of five cases. (2008)
  • 著者名/発表者名: Kojima M, et. al.
  • 雑誌名: Pathol Res Pract. 204 ページ: 185-190
  • 査読あり
• [雑誌論文] Definition, Diagnosis, and Management of Intravascular Large B Cell Lymphoma : Proposals and Perspectives From an International Consensus Meeting (2007)
  • 著者名/発表者名: Ponzoni M, Ferreri AJ, Campo E, Facchetti F, Mazzucchelli L, Yoshino T, Murase T, Pileri SA, Doglioni C, Zucca E, Cavalli F, Nakamura S.
  • 雑誌名: J Clin Oncol 25(21) ページ: 3168-73
  • 査読あり
• [雑誌論文] Intravascular large B-cell lymphoma : the heterogeneous clinical manifestations of its classical and hemophagocytosis-related forms (2007)
  • 著者名/発表者名: Nakamura S, Murase T, Kinoshita T.
  • 雑誌名: Haematologica 92(4) ページ: 434-6
  • 査読あり
• [雑誌論文] Intravascular large B-cell lymphoma (IVLBCL) : a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5 (2007)
  • 著者名/発表者名: Murase T, Yamaguchi M, Suzuki R, Okamoto M, Sato Y, Tamaru JI, Kojima M, Miura I, Mori N, Yoshino T, Nakamura S.
  • 雑誌名: Blood 109(2) ページ: 478-85
  • 査読あり
• [雑誌論文] Cytotoxic molecule expression is predictive of prognosis in Hodgkin's-like anaplastic large cell lymphoma (2007)
  • 著者名/発表者名: Asano N, Suzuki R, Matsuo K, Kagami Y, Ishida F, Tamaru JI, Jin GS, Sato Y Shimoyama Y, Yoshino T, Morishima Y, Nakamura S.
  • 雑誌名: Histopathology 50(6) ページ: 705-15
  • 査読あり
• [雑誌論文] Primary hepatic follicular lymphoma: a case report and discussion of chemotherapy and favorable outcomes. (2007)
  • 著者名/発表者名: Gomyo H, et. al.
  • 雑誌名: J Clin Exp Hematop. 47 ページ: 73-77
  • 査読あり
• [雑誌論文] Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group a study of 96 patients. (2007)
  • 著者名/発表者名: Oyama T, et. al.
  • 雑誌名: Clin Cancer Res 13 ページ: 5124-5132
  • 査読あり
• [雑誌論文] Wilms' tumor 1 message and protein expression in bone marrow failuresyndrome and acute leukemia. (2007)
  • 著者名/発表者名: Iwasaki T, et. al.
  • 雑誌名: Pathol Int. 57 ページ: 645-651
  • 査読あり
• [雑誌論文] A novel AF10-CALM fusion transcript in gamma/delta-T cell type lymphoblastic lymphoma. (2007)
  • 著者名/発表者名: Ashihara E, et. al.
  • 雑誌名: Am J Hematol. 82 ページ: 859-860
  • 査読あり
• [雑誌論文] Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting. (2007)
  • 著者名/発表者名: Ponzoni M, et. al.
  • 雑誌名: J Clin Oncol. 25 ページ: 3168-3173
  • 査読あり
• [雑誌論文] Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. (2007)
  • 著者名/発表者名: Ishii E, et. al.
  • 雑誌名: Int J Hematol. 86 ページ: 58-65
  • 査読あり
• [雑誌論文] EBV-related reactive lymphoproliferative disorders in middle-aged or elderly patients presenting with atypical features. A clinicopathological study of six cases. (2007)
  • 著者名/発表者名: Kojima M, et. al.
  • 雑誌名: Pathol Res Pract. 203 ページ: 587-591
  • 査読あり
• [雑誌論文] Trisomy 3 is a specific genomic aberration of t(14;18) negative follicular lymphoma. (2007)
  • 著者名/発表者名: Tagawa H, et. al.
  • 雑誌名: Leukemia 21 ページ: 2549-2551
  • 査読あり
• [雑誌論文] Intravascular large B-cell lymphoma: the heterogeneous clinical manifestations of its classical and hemophagocytosis-related forms. (2007)
  • 著者名/発表者名: Nakamura S, et. al.
  • 雑誌名: Haematologica 92 ページ: 434-436
• [雑誌論文] Hodgkin-like anaplastic large cell lymphoma (previously designated in the REAL) has same immunophenotypic features to classical Hodgkin lymphoma. (2007)
  • 著者名/発表者名: Tamaru J, et. al.
  • 雑誌名: Leuk Lymphoma. 48 ページ: 1127-1138
  • 査読あり
• [雑誌論文] API2-MALT1 chimeric transcript-positive gastroduodenal MALT lymphoma with subsequent development of adenocarcinoma as a collision tumour over a clinical course of 7 years. (2007)
  • 著者名/発表者名: Isaka T, et. al.
  • 雑誌名: Histopathology 51 ページ: 119-123
  • 査読あり
• [雑誌論文] Histological diversity of reactive and atypical proliferative lymph node lesions in systemic lupus erythematosus patients. (2007)
  • 著者名/発表者名: Kojima M, et. al.
  • 雑誌名: Pathol Res Pract. 203 ページ: 423-431
  • 査読あり
• [雑誌論文] Cytotoxic molecule expression is predictive of prognosis in Hodgkin's-like anaplastic large cell lymphoma. (2007)
  • 著者名/発表者名: Asano N, et. al.
  • 雑誌名: Histopathology. 50 ページ: 705-715
  • 査読あり
• [図書] Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)WHO Classification of Tumours of Haematopietic and Lymphoid Tissues. (2008)
  • 著者名/発表者名: Isaacson PG, Chott A, Nakamura S, Muller-Hermelink HK, Harris NL, Swerdlow SH.
  • 出版者: IARS Press, Lyon(Swedlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds.)
• [図書] WHO Classification of Tumours of Haematopietic and Lymphoid Tissues(Swedlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds.) (2008)
  • 著者名/発表者名: Nakamura S, Jaffe ES, Swerdlow SH.
  • 出版者: IARS Press, Lyon
• [図書] WHO Classification of Tumours of Haematopietic and Lymphoid Tissues(Swedlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds.) (2008)
  • 著者名/発表者名: Nakamura S, Ponzoni M, Campo E.
  • 出版者: IARS Press, Lyon
• [図書] Muller-Hermelink HK, Jaffe ES.Peripheral T-cell lymphoma, not otherwise specified.WHO Classification of Tumours of Haematopietic and Lymphoid Tissues(Swedlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW eds.) (2008)
  • 著者名/発表者名: Pileri SA, Ralfkiaer E, Weisenburger DD, Nakamura S, Sng I, Nakamura S
  • 出版者: IARS Press, Lyon
• [図書] WHO Classification of Tumours of Haematopietic and Lymphoid Tiss ues. (2008)
  • 著者名/発表者名: Nakamura S, et al.
  • 総ページ数: 439
  • 出版者: IARS Press, Lyon