Molecular Pathology of Mediastinal Lymphoproliferative Disoders of the Adult

• Project/Area Number: 24590422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Nagoya City University
• Principal Investigator: INAGAKI Hiroshi 名古屋市立大学, 医学(系)研究科(研究院), 教授 (30232507)
• Co-Investigator(Kenkyū-buntansha): YAMADA Seiji 名古屋市立大学, 大学院医学研究科, 助教 (00566870) ; MASAKI Ayako 名古屋市立大学, 大学院医学研究科, 助教 (40648044)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 悪性リンパ腫 / 成人 / 縦隔 / 分子病理学 / リンパ増殖性疾患

Outline of Final Research Achievements

Molecular pathological studies were was performed for adult mediastinal lymphoproliferative disorders in the Asia. In thymic MALT lymphoma, a frequent gene methylation was detected. In particular, p14 (ARF) gene methylation was associated with a larger tumor size, suggesting a role in tumor progression. In primary mediastinal large B-cell lymphoma, frequent abnormalities of CIITA and PDE5A genes have been reported from Western countries. We studied these abnormalities using FISH technique, although no significant abnormalities were found. This may suggest genetic difference between the Western and Asian cases. Progress of thymic MALT lymphoma in these 20 years was studied. After a critical discussion with distinguished hematopathologists, I published the results as the first author in the 4th WHO classification of thymic tumors.

Research Products

• [Journal Article] CD30-positive primary bone marrow lymphoma mimicking Hodgkin lymphoma (2015)
  • Author(s): Suzuki T, Kusumoto S, Masaki A, Ishida T, Inagaki H, Iida S, Mori F.
  • Journal Title: International Journal of Hematology Volume: 印刷中 Issue: 2 Pages: 109-11
  • DOI: 10.1007/s12185-014-1714-8
  • Peer Reviewed
• [Journal Article] Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy (2015)
  • Author(s): Totani H, Kusumoto S, Ishida T, Masuda A, Yoshida T, Ito A, Ri M, Komatsu H, Murakami S, Mizokami M, Ueda R, Niimi A, Inagaki H, Tanaka Y, Iida S.
  • Journal Title: International Journal of Hematology Volume: 印刷中 Issue: 4 Pages: 398-404
  • DOI: 10.1007/s12185-015-1750-z
  • Peer Reviewed
• [Journal Article] Prognostic significance of tryptophan catabolism in adult T-cell leukemia/lymphoma (2015)
  • Author(s): Masaki A, Ishida T. Maeda Y, Suzuki S, Ito S, Takino H, Ogura H, Totani H, Yoshida T, Kinoshita S, Narita T, Ri M, Kusumoto S, Inagaki A, Komatsu H, Niimi A, Ueda R, Utsunomiya A, Inagaki H, Iida S
  • Journal Title: Clinial Cancer Reseach Volume: 印刷中
  • NAID: 130005130183
  • Peer Reviewed
• [Journal Article] Distinctive Immunoglobulin VH Gene Features of Cutaneous Marginal Zone Lymphomas in Asian Cases (2014)
  • Author(s): Ge Y, Takino H, Sato F, Yamada S, Masaki A, Fujiyoshi Y, Hattori H, Morita A, Kuo T-t, Inagaki H
  • Journal Title: British Journal of Dermatology Volume: 170 Pages: 735-737
  • Peer Reviewed
• [Journal Article] Histiocytic sarcoma of the bile duct (2014)
  • Author(s): Miyabe K, Masaki A, Nakazawa T, Ando T, Hayashi K, Naitoh I, Okumura F, Shimizu S, Kondo H, Yoshida M, Yamashita H, Umemura S, Hori Y, Ge Y, Ohara H, Joh T, Inagaki H
  • Journal Title: Internal Medicine Volume: 53 Pages: 707-712
  • NAID: 130003392738
  • Peer Reviewed
• [Journal Article] Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model (2014)
  • Author(s): Mori F, Ishida T, Ito A, Sato F, Masaki A, Narita T, Suzuki S, Yamada T, Takino H, Ri M, Kusumoto S, Komatsu H, Hishizawa M, Imada K, Takaori-Kondo A, Niimi A, Ueda R, Inagaki H, Iida S
  • Journal Title: European Journal of Haematology Volume: 92 Issue: 3 Pages: 219-228
  • DOI: 10.1111/ejh.12231
  • Peer Reviewed
• [Journal Article] Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-CCR4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma (2014)
  • Author(s): Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, Fujimoto K, Yamamoto K, Miyamoto T, Uike N, Tanimoto M, Tsukasaki K, Ishizawa K, Suzumiya J, Inagaki H, Tamura K, Akinaga S, Tomonaga M, Ueda R.
  • Journal Title: Journal of Clinical Oncology Volume: 32 Pages: 1157-1163
  • Peer Reviewed
• [Journal Article] Prognostic impact of miR-145 down-regulation in adult T-cell leukemia/ lymphoma (2014)
  • Author(s): Xia H, Yamada S, Aoyama M, Sato F, Masaki A, Ge Y, Ri M, Ishida T, Ueda R, Utsunomiya A, Asai K, Inagaki H
  • Journal Title: Human Pathology Volume: 45 Pages: 1192-1198
  • Peer Reviewed
• [Journal Article] 悪性リンパ腫の分類：消化管悪性リンパ腫の分子病態 (2014)
  • Author(s): 正木彩子、稲垣 宏
  • Journal Title: 胃と腸 Volume: 49 Pages: 582-590
• [Journal Article] 脳出血で死亡した小児特発性血小板減少性紫斑病の1例 (2014)
  • Author(s): 藤井香那, 伊藤洋平, 正木彩子, 山田勢至, 藤吉行雄, 服部日出男, 稲垣宏, 亀井美智, 伊藤康彦, 斎藤伸治, 西川祐介, 山田和雄, 岡本尚
  • Journal Title: 現代医学 Volume: 62
• [Journal Article] コレステロール血栓症の１剖検例 (2014)
  • Author(s): 藤吉行雄, 藤井香那, 伊藤洋平, 山田勢至, 正木彩子, 服部日出男, 稲垣宏
  • Journal Title: 現代医学 Volume: 62 Pages: 113-116
• [Journal Article] 反応性リンパ節病変と悪性リンパ腫：鑑別の実際 (2014)
  • Author(s): 稲垣宏
  • Journal Title: 臨床血液 Volume: 55 Pages: 1989-1998
  • NAID: 130004696092
• [Journal Article] Global real-time quantitative reverse transcription-polymerase chain reaction detecting proto-oncogenes associated with 14q32 chromosomal translocation as a valuable marker for predicting survival in multiple myeloma. (2013)
  • Author(s): Inagaki A, Tajima E, Uranishi M, Totani H, Asao Y, Ogura H, Masaki A, Yoshida T, Mori F, Ito A, Yano H, Ri M, Kayukawa S, Kataoka T, Kusumoto S, Ishida T, Hayami Y, Hanamura I, Komatsu H, Inagaki H, Matsuda Y, Ueda R, Iida S.
  • Journal Title: Leukemia Research Volume: 37 (12) Issue: 12 Pages: 1648-1655
  • DOI: 10.1016/j.leukres.2013.09.026
  • Peer Reviewed
• [Journal Article] Thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a gene methylation study. (2013)
  • Author(s): Takino H, Li C, Yamada S, Sato F, Masaki A, Fujiyoshi Y, Hattori H, Inagaki H.
  • Journal Title: Leukemia & Lymphoma Volume: 54 (8) Issue: 8 Pages: 1742-1746
  • DOI: 10.3109/10428194.2013.765563
  • Peer Reviewed
• [Journal Article] Autologous Tax-specific CTL therapy in a primary adult T cell leukemia/lymphoma cell-bearing NOD/Shi-scid, IL-2Rγnull mouse model. (2013)
  • Author(s): Masaki A, Ishida T, Suzuki S, Ito A, Mori F, Sato F, Narita T, Yamada T, Ri M, Kusumoto S, Komatsu H, Tanaka Y, Niimi A, Inagaki H, Iida S, Ueda R.
  • Journal Title: The journal of Immunology Volume: 191 (1) Issue: 1 Pages: 135-144
  • DOI: 10.4049/jimmunol.1202692
  • Peer Reviewed
• [Journal Article] Bath-PUVA Therapy Decreases Infiltrating CCR4-Expressing Tumor Cells and Regulatory T Cells in Patients With Mycosis Fungoides. (2013)
  • Author(s): Kato H
  • Journal Title: Clin Lymphoma Myeloma Leuk. Volume: Epub ahead Issue: 3 Pages: 273-280
  • DOI: 10.1016/j.clml.2012.12.002
  • Peer Reviewed
• [Journal Article] Stevens-Johnson Syndrome associated with mogamulizumab treatment of adult T-cell leukemia / lymphoma. (2013)
  • Author(s): Ishida T
  • Journal Title: Cancer Sci. Volume: 104 Issue: 5 Pages: 647-50
  • DOI: 10.1111/cas.12116
  • Peer Reviewed
• [Journal Article] Angioimmunoblastic T-cell lymphoma mice model. (2013)
  • Author(s): Sato F
  • Journal Title: Leuk Res. Volume: 37 Issue: 1 Pages: 21-7
  • DOI: 10.1016/j.leukres.2012.09.009
  • Peer Reviewed
• [Journal Article] Bath-PUVA therapy decreases infiltrating CCR4-expressing tumor cells and regulatory T cells in patients with mycosis fungoides (2013)
  • Author(s): Kato H, Saito C, Ito E, Furuhashi T, Nishida E, Ishida T, Ueda R, Inagaki H, Morita A.
  • Journal Title: Clin Lymphoma Myeloma Leuk Volume: なし
• [Journal Article] Thymic Extranodal Marginal Zone Lymphoma of Mucosa-associated Lymphoid Tissue: A Gene Methylation Study (2013)
  • Author(s): Takino H, Li C, Yamada S, Sato F, Masaki A, Fujiyoshi Y, Hattori H, Inagaki H.
  • Journal Title: Leuk Lymphoma Volume: なし
  • Peer Reviewed
• [Journal Article] Potent antitumor effects of bevacizumab in a microenvironment-dependent human lymphoma mouse model (2012)
  • Author(s): Mori F, Ishida T, Ito A, Sato F, Masaki A, Takino H, Ri M, Kusumoto S, Komatsu H, Ueda R, Inagaki H, Iida S
  • Journal Title: Blood Cancer J. Volume: 51 Pages: 3125-3129
  • Peer Reviewed
• [Journal Article] Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favourable prognosis : a study of the Osaka Lymphoma Study Group (2012)
  • Author(s): Wada N, Zaki MA, Kohara M, Ogawa H, et al.(12人中4番)
  • Journal Title: Histopathology Volume: 60 Issue: 6 Pages: 924-932
  • DOI: 10.1111/j.1365-2559.2011.04161.x
  • Peer Reviewed
• [Journal Article] Analysis of VH gene rearrangement and somatic hypermutation in type 1 autoimmune pancreatitis (2012)
  • Author(s): Okumura F, Sakuma H, Nakazawa T, Hayashi K, Naitoh I, Miyabe K, Yoshida M, Yamashita H, Ohara H, Inagaki H, Joh T.
  • Journal Title: Pathology international Volume: 62 Issue: 5 Pages: 318-323
  • DOI: 10.1111/j.1440-1827.2012.02788.x
  • NAID: 10031185207
  • Peer Reviewed
• [Journal Article] Cancer/testis antigens are novel targets of immunotherapy for adult T cell leukemia/lymphoma (2012)
  • Author(s): Nishikawa H.
  • Journal Title: Blood Volume: 119(13) Issue: 13 Pages: 3097-104
  • DOI: 10.1182/blood-2011-09-379982
  • Peer Reviewed
• [Journal Article] Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma a multicenter phase II study (2012)
  • Author(s): Ishida T.
  • Journal Title: J Clin Oncol Volume: 30(8) Issue: 8 Pages: 837-42
  • DOI: 10.1200/jco.2011.37.3472
  • Peer Reviewed
• [Journal Article] Characterization of chromosomal aberrations in thymic MALT lymphoma. (2012)
  • Author(s): Kominato S, Nakayama T, Sato F, Yamada S, Xia H, Fujiyoshi Y, Hattori H, Inagaki H.
  • Journal Title: Pathol Int. Volume: 62 Issue: 2 Pages: 93-98
  • DOI: 10.1111/j.1440-1827.2011.02764.x
  • NAID: 10031185173
  • Peer Reviewed
• [Journal Article] Tax is a potential molecular target for immunotherapy of adult T-cell leukemia/lymphoma. (2012)
  • Author(s): Suzuki S
  • Journal Title: Cancer Sci. Volume: 103 Issue: 10 Pages: 1764-73
  • DOI: 10.1111/j.1349-7006.2012.02371.x
  • Peer Reviewed
• [Journal Article] Forkhead box P1 overexpression and its clinicopathological significance in peripheral T-cell lymphoma, not otherwise specified (2011)
  • Author(s): Yamada S, Sato F, Xia H, Takino H, Kominato S, Ri M, Ishida T, Iida S, Inagaki H, Yamada K.
  • Journal Title: Hum Pathol Volume: 2 Issue: 8 Pages: 570-575
  • DOI: 10.1016/j.humpath.2011.10.013
  • Peer Reviewed
• [Presentation] 反応性リンパ節病変と悪性リンパ腫：鑑別の実際 (2014)
  • Author(s): 稲垣宏
  • Organizer: 第76回日本血液学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-10-31 – 2014-11-02
  • Invited
• [Presentation] 成人T細胞性白血病/リンパ腫におけるindoleamine 2,3-diozygenaseの臨床的意義 (2014)
  • Author(s): 正木彩子、石田高司、前田康博、稲垣淳、鈴木進、伊藤旭、成田朋子、榊原健夫、滝野寿、李政樹、楠本茂、小松弘和、上田龍三、稲垣宏、宇都宮與、飯田真介
  • Organizer: 第54回日本リンパ網内系学会
  • Place of Presentation: 山形国際ホテル
  • Year and Date: 2014-06-19 – 2014-06-21
• [Presentation] miR-145 down-regulationが成人T細胞性白血病/リンパ腫の予後に与える影響 (2014)
  • Author(s): 正木彩子、滝野寿、青山峰芳、夏洪晶、山田勢至、佐藤文彦、葛岩、李政樹、石田高司、上田龍三、宇都宮與、浅井清文、稲垣宏
  • Organizer: 第54回日本リンパ網内系学会
  • Place of Presentation: 山形国際ホテル
  • Year and Date: 2014-06-19 – 2014-06-21
• [Presentation] クローン病と鑑別困難で抗TNFa抗体投与後に増悪したNK/T cell lymphoma, nasal typeの１例 (2014)
  • Author(s): 正木彩子、増田有彩、藤井香那、伊藤洋平、葛岩、榊原健夫、滝野寿、山田勢至、楠本茂、藤吉行雄、服部日出雄、稲垣宏
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 脳出血で死亡した小児特発性血小板減少性紫斑病の１剖検例 (2014)
  • Author(s): 藤井香那, 山田勢至, 正木彩子, 伊藤洋平, 榊原健夫, 滝野寿, 藤吉行雄, 服部日出男, 稲垣宏
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Primary leptomeningeal diffuse large B-cell lymphomaの1剖検例 (2014)
  • Author(s): 山田勢至、正木彩子、森芙実子、高田幸児、藤井香那、伊藤洋平、葛岩、榊原健夫、滝野寿、藤吉行雄、服部日出男、稲垣宏
  • Organizer: 第103回日本病理学会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Analysis of immunoglobulin VH genes in cutaneous marginal zone B-cell lymphoma (2013)
  • Author(s): 葛 岩、佐久間英規、正木彩子、山田勢至、佐藤文彦、稲垣宏
  • Organizer: 第53回日本リンパ網内系学会総会
  • Place of Presentation: 国立京都会館（京都府京都市）
• [Presentation] The usefulness of lip biopsy for the diagnosis of AL amyloidosis: A retrospective analysis (2013)
  • Author(s): Suzuki T, Kusumoto S, Masuda A, Uegaki S, Yoshida T, Mori F, Ito A, Ri M, Ishida T, Komatsu H, Inagaki H, Niimi A, Iida S.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌（北海道札幌市 ）
• [Presentation] Clinical significance of indoleamine 2,3-dioxygenase (IDO) expression in ATL (2013)
  • Author(s): Masaki A, Ishida T, Masuda A, Inagaki A, Suzuki S, Ito A, Mori F, Sato F, MNarita T, Ri M, Kusumoto S, Komatsu H, Niimi A, Ueda R, Inagaki H, Utsunomiya A, Iida S.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: ロイトン札幌（北海道札幌市 ）
• [Presentation] 患者由来Tax特異的CTLを用いたATLマウスモデルに対する免疫療法 (2013)
  • Author(s): 正木彩子、石田高司、鈴木 進、森 芙美子、伊藤 旭、林 直樹、野田晴菜、榊原健夫、山田勢至、佐藤文彦、滝野 寿、服部日出雄、藤吉行雄、稲垣宏
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌、さっぽろ芸文館（北海道札幌市 ）
• [Presentation] 口蓋に生じたFollicular lymphoid hyperplasiaの一例 (2013)
  • Author(s): 佐藤文彦、山田勢至、正木彩子、滝野 寿、榊原健夫、藤吉行雄、服部日出雄、稲垣宏
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌、さっぽろ芸文館（北海道札幌市 ）
• [Presentation] 悪性リンパ腫診断 update 2012 (2012)
  • Author(s): 稲垣宏
  • Organizer: 病理学教育セミナー
  • Place of Presentation: 名古屋大学（名古屋）
  • Invited
• [Presentation] Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CCR4 Antibody, in Patients with Relapsed Peripheral and Cutaneous T-Cell Lymphoma (2012)
  • Author(s): Ishida T, Inagaki H, et al.
  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Georgia World Congress Center (Atlanta, USA)
• [Presentation] T細胞性腫瘍に対する抗CCR4抗体医薬の開発と評価 (2012)
  • Author(s): 稲垣宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京）
  • Invited
• [Presentation] 唾液腺腫瘍の分子病理学的解析とその臨床病理学的意義 (2012)
  • Author(s): 宮部悟、長尾俊孝、稲垣宏
  • Organizer: 第101回日本病理学会総会/唾液腺腫瘍病理研究会
  • Place of Presentation: 京王プラザホテル（東京）
  • Invited
• [Presentation] 成人T細胞性白血病/リンパ腫におけるFOXP1遺伝に発現の臨床病理学的意義 (2012)
  • Author(s): 山田勢至、夏洪晶、佐藤文彦、藤吉行雄、服部日出雄、稲垣宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] 長期間保存後もフローサイトメトリー可能な細胞保存液の検討 (2012)
  • Author(s): 林直樹、佐藤文彦、山田勢至、夏洪晶、榊原健夫、滝野寿、藤吉行雄、服部日出雄、稲垣宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] 血管免疫芽球性T細胞性リンパ腫モデルマウスの樹立 (2012)
  • Author(s): 佐藤文彦、林直樹、夏洪晶、山田勢至、藤吉行雄、服部日出雄、稲垣宏
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京）
• [Presentation] 辺縁帯リンパ腫における形質細胞分化の意義と胸腺MALTリンパ腫 (2012)
  • Author(s): 稲垣宏
  • Organizer: 第52回日本リンパ網内系学会総会
  • Place of Presentation: 福島ビューホテル（福島）
  • Invited
• [Presentation] Potent antitumor effects of bevacizumab in a microenvironment-dependent human ATL mouse model (2012)
  • Author(s): Mori F, Inagaki H, et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
• [Presentation] Autologous Tax-specific CTL therapy in a primary ATL cell-bearing NOG mouse model (2012)
  • Author(s): Masaki A, Inagaki H, et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
• [Book] Thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (Chapter 3-6B). WHO Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart, 4th ed. Ed. Travis WD, Brambilla E, Burke AP, Maex A, Nicholson AG (2015)
  • Author(s): Inagaki H, Chan JKC, Jaffe ES, Harris NL, Moller P, Nakamura S
  • Total Pages: 412
  • Publisher: WHO Press Lyon
• [Book] 縦隔腫瘍・胸膜腫瘍 腫瘍病理鑑別診断アトラス (2014)
  • Author(s): 正木彩子、稲垣 宏
  • Total Pages: 289
  • Publisher: 文光堂
• [Book] 癌診療指針のための病理診断プラクティス 食道癌・胃癌/上部消化管リンパ腫 (2012)
  • Author(s): 稲垣宏，楠本茂，片岡洋望
  • Total Pages: 307
  • Publisher: 中山書店
• [Remarks] 名古屋市立大学大学院医学研究科臨床病態病理学ホームページ
  • URL: http://www.med.nagoya-cu.ac.jp/patho2.dir/mysite1/index.html
• [Remarks] 名古屋市立大学大学院医学研究科臨床病態病理学（病理学II）ホームページ
  • URL: http://www.med.nagoya-cu.ac.jp/patho2.dir/mysite1/index.html