Analyses of epigenetic mechanism of lymphomagenesis/leukemogenesis

• Project/Area Number: 19590349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Okayama University
• Principal Investigator: OKA Takashi Okayama University, 大学院・医歯薬学総合研究科, 助教 (50160651)
• Co-Investigator(Kenkyū-buntansha): YOSHINO Tadashi 岡山大学, 大学院・医歯薬学総合研究科, 教授 (70183704) ; OUCHIDA Mamoru 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (80213635)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: エピジェネテイックス / 悪性リンパ腫 / 白血病 / ATLL / MALTリンパ腫 / HTLV-I / H.pylori / DNAメチル化 / MALT lymphoma

Research Abstract

悪性腫瘍の発症機構に関する研究は、これまで癌遺伝子、癌抑制遺伝子の構造異常などを伴うゼネテイックな変化に注目して研究が進められてきた。それに対し近年遺伝子の構造異常を伴わないエピジェネテイックな機構による発癌が注目されてきている。我々は造血器腫瘍の発症機構をとくにエピジェネテイックな機構に注目し解析を行い、HTLV-I, H.pyloriの感染によって異常なDNAメチル化が誘導・蓄積することが造血器腫瘍発症に重要であることを見いだした。これらの知見を元に造血器腫瘍を高感度に早期発見・早期診断することが可能になると期待される。

Research Products

• [Journal Article] Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas (2008)
  • Author(s): Sato Y, Ichimura K, Tanaka T, Takata K, Morito T, Sato H, Kondo E, Yanai H, Ohara N, Oka T, Yoshino T
  • Journal Title: J Clin Pathol 61(3) Pages: 377-81
  • Peer Reviewed
• [Journal Article] リンパ系腫瘍におけるDNAメチル化異常 (2008)
  • Author(s): 岡剛史、吉野正
  • Journal Title: 血液フロンテイア 18(11) Pages: 1-9
• [Journal Article] Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas. (2008)
  • Author(s): Sato Y, Oka T, Yoshino T., et al
  • Journal Title: J Clin Pathol. 61 Pages: 377-381
  • Peer Reviewed
• [Journal Article] リンパ系腫瘍におけるDNAメチル化異常 (2008)
  • Author(s): 岡 剛史, 吉野正
  • Journal Title: 血液フロンティア 18 Pages: 1-9
• [Journal Article] Down-regulation of drs Mrna is associated with the progression of adult T-cell leukemia/lymphoma (2007)
  • Author(s): Shimakage, M., Inoue, N., Oshima,K., Kawahara, K., Yamamoto, N., Oka, T., Tambe, Y.,Yasui, K., Matsumoto, K., Yutsudo, M., and Inoue, H
  • Journal Title: Int. J. Oncol 30(6) Pages: 1343-8
  • Peer Reviewed
• [Journal Article] Immunoelectron-microscopic study of CD4- and CD8-positive lymphocytes from healthy donors seropositive for human T-lymphotropic virus type I (2007)
  • Author(s): Ohtsuki Y., Oka T., Manabe Y., Takeuchi T., Lee G, H., Furihata M., Yoshino T., Taguchi H. and Miyoshi I
  • Journal Title: Biomedical Res 18(2) Pages: 83-88
  • Peer Reviewed
• [Journal Article] Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas (2007)
  • Author(s): Sato Y, Ichimura K, Tanaka T, Takata K, Morito T, Sato H, Sato Y, Kondo E, Yanai H, Ohara N, Oka T, Yoshino T
  • Journal Title: J Clin Pathol 61 Pages: 377-381
  • Peer Reviewed
• [Journal Article] High frequent gene silencing of hematopoietic cell specific protein tyrosine phosphatase SHP1 in hematopoietic cell malignancies (2007)
  • Author(s): T. Oka., M. Ouchida., M. Tanimoto., K. Shimizu and T. Yoshino.
  • Journal Title: Int. J. Med. Biol. Fronteiers 11 Pages: 11-42
  • Peer Reviewed
• [Journal Article] High frequent gene silencing of hematopoietic cell specific protein tyrosine phosphatase SHP1 in hematopoietic cell malignancies. (2007)
  • Author(s): T. Oka., M. Ouchida., M. Tanimoto., K. Shimizu and T. Yoshino.
  • Journal Title: Int. J. Med. Biol. Front。 11 Pages: 11-42
  • Peer Reviewed
• [Journal Article] Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas. (2007)
  • Author(s): Sato Y, Ichimura K, Ohara N, Oka T, Yoshino T., et. al.
  • Journal Title: J Clin Pathol. 61 Pages: 377-381
  • Peer Reviewed
• [Journal Article] Immunoelectron-microscopic study of CD4-and CD8-positive lymphocytes from healthy donors seropositive for human T-lymphotropic virus type I., (2007)
  • Author(s): Ohtsuki Y., Oka T., Manabe Y., Takeuchi T., Lee G, H., et. al.
  • Journal Title: Biomedical Res. 18 Pages: 83-88
  • Peer Reviewed
• [Journal Article] Down-regulation of drs mRNA is associated with the progression of adult T-cell leukemia/lymphoma. (2007)
  • Author(s): Shimakage, M., Inoue, N., Oshima, K., Kawahara, K., Yamamoto, N., Oka, T., Tambe, Y., Yasui, K., Matsumoto, K., Yutsudo, M., and Inoue. H.
  • Journal Title: Int. J. Oncol., 30 Pages: 1343-11348
  • Peer Reviewed
• [Journal Article] Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma
  • Author(s): Takami Kondo, Takashi Oka, Hiaki Sato, Yoko Shinnou, Kana Washio, Masayuki Takano, Toshiaki Morito, Katsuyoshi Takata, Nobuya Ohara, Mamoru Ouchida, Kenji Shimizu, and Tadashi Yoshino
  • Journal Title: Int. J. Oncol (In press)
  • Peer Reviewed
• [Journal Article] Duodenal and nodal follicular lymphomas are distinct : the former lacks activation-induced cytidine deaminase an folliculardendritc cells despite ngoing smatic hypermutaion
  • Author(s): Takata K, Sato Y, Nakamura N, Kikuchi Y.Y, Ichimura K, Tanaka T, Morito T, Tamura M, Oka T, Kondo E, Okada H, Tari A and Yoshino T
  • Journal Title: Mod. Pathol (In press)
  • Peer Reviewed
• [Presentation] 悪性腫瘍とエピジェネティックス; 造血器腫瘍発症・進展におけるエピジェネティック異常 (2008)
  • Author(s): 岡剛史
  • Organizer: 第40回日本臨床分子形態学会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-04
• [Presentation] 悪性腫瘍とエピジェネテイツクス ; 造血器腫瘍発症・進展におけるエピジェネテイ (2008)
  • Author(s): 岡 剛史
  • Organizer: 第40回日本臨床分子形態学会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-04
• [Presentation] 成人T細胞白血病/リンパ腫(ATLL)における特異的DNAメチル化と病態・予後との相関 (2008)
  • Author(s): 佐藤妃映、岡 剛史、神農陽子、鷲尾佳奈、高野正幸、高田尚良、守都敏晃、田村麻衣子、黄 新剛、大西尚子、大内田守、大島孝一、宇都宮與、高橋聖之、谷本光音、吉野正
  • Organizer: 第1回HTLV1研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-20
• [Presentation] Identification of the specific genes regulated by epigenetic mechanism during osteoblastic/adipocytic differentiations in human mesenchymal stem cells (2008)
  • Author(s): Masayuki Takano, Takashi Oka, Yoko Shinnou, Takami Kondo, Hiaki Sato, Kana Washio, Toshiaki Morito, Katsuyoshi Takata, Ichiro Murakami, Nobuya Ohara, Tohru Nakanishi , Tadashi Yoshino
  • Organizer: 第31回日本分子生物学会、第81回日本精化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] Effect of nitrogen containing bisphosphonate on osteoblast differentiation of rat mesenchymal stem cell (2008)
  • Author(s): Kaduko Kurokawa, Hirofumi Fujita, Eri Oyanagi, Takashi Oka, Kozo Utsumi and Junzo Sasaki
  • Organizer: 第31回日本分子生物学会、第81回日本精化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] 成人T細胞白血病/リンパ腫(ATLL)におけるDNAメチル化の解析 (2008)
  • Author(s): 佐藤妃映、岡剛史、神農陽子、鷲尾佳奈、高田尚良、守都敏晃、田村麻衣子、黄 新剛、北村雄太、大原信哉、村上一郎、清水憲二、大内田守、谷本光音、大島孝一、宇都宮與、高橋聖之、吉野正
  • Organizer: 第31回日本分子生物学会、第81回日本精化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] Immunohistochemical analyses of PTPN6(SHP1) on Langerhnas cell histiocytosis (2008)
  • Author(s): Ichiro Murakami, Takashi Oka, Hiaki Sato, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinno, Nobuya Ohara, Eisaku Kondo, Kiyoshi Takahasi, akehiro Tanaka, Tdashi Yoshino
  • Organizer: 67^<th> Annual meetin of the Japanese Cancer association
  • Place of Presentation: Nagoya
• [Presentation] Molecular Pathological examination on aberrant expression of cyclinD1 and CD79a in multiple myeloma cell lines (2008)
  • Author(s): Takata K., Oka T., Tanaka T., Sato H., Murakami I., Morito T., Takano M., Washio K., Otsuki T., and YoshinoT
  • Organizer: 67^<th> Annual meeting of the Japanese Cancer association
  • Place of Presentation: Nagoya
• [Presentation] IMMUNOHISTOCHEMICAL ANALYSES OF PTPN6 (SHP1) ON LANGERHANS CELL HISTIOCYTOSIS (2008)
  • Author(s): Ichiro Murakami, Takashi Oka, Hiaki Sato, Yuta Kitamura, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinno, Masayuki Takano, Kana Washio, Xingang Huang, Maiko Tamura, Naoko Ohnishi, Koichi Ichimura,Yasuharu Sato, Hiroyuki Yanai, Nobuya Ohara, Eisaku Kondo, Kiyoshi Takahashi, Takehiro Tanaka, Jean Gogusev, FranciJaubert, Akira Morimoto, Shinsaku Imashuku, Tadaatsu Akagi, Tadashi Yoshino
  • Organizer: Annual Meeting of the Histiocyte Society
  • Place of Presentation: Germany
• [Presentation] 成人T細胞白血病/リンパ腫(ATLL)における特異的DNAメチル化と病態との関連 (2008)
  • Author(s): 佐藤妃映、岡 剛史、神農陽子、鷲尾佳奈、高田 尚良、守都 敏晃、大原信哉、大内田守、大島孝一、谷本光音、宇都宮與、高橋聖之、吉野正
  • Organizer: H20リンパ網内系学会
  • Place of Presentation: 札幌
• [Presentation] Immunohstochemical analysis of PTPN6 (SHP-1) on Langerhans cell histiocytosis (2008)
  • Author(s): Ichiro Murakami, Takashi Oka, Tadashi Yoshino
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 金沢
• [Presentation] 成人T細胞白血病/リンパ腫(ATLL)における特異的DNAメチル化と予後との相関について (2008)
  • Author(s): 佐藤妃映、岡剛史、神農陽子、鷲尾佳奈、高野正幸、高田尚良, 守都敏晃,大原信哉、大内田守,大島孝一、宇都宮與、高橋聖之、吉野正
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 金沢
• [Presentation] T cellリンパ腫におけるSHP1の発現低下と、脱メチル化処理による発現回復がSignal pathwayに及ぼす変化 (2008)
  • Author(s): 神農陽子、岡剛史、佐藤妃映、高野正幸、村上一郎、鷲尾佳奈、高田尚良、守都敏晃、黄新剛、田村麻衣子、大西尚子、吉野正
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 金沢
• [Presentation] 樹状細胞と樹状マクロファージから視た胸腺腫のWHO分類 (2008)
  • Author(s): 高橋聖之、富坂竜矢、西川由利子、佐藤妃映、岡剛史、吉野正
  • Organizer: 第97回日本病理学会
  • Place of Presentation: 金沢
• [Presentation] Immunohistochinalanalysis of PTPN6(SHP1) on Langerhans cell histiocytosis (2007)
  • Author(s): Ichiro Murakami, Takashi Oka , Hiaki Sato, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinnou, Kan Washo, Masayuki Takano, Nobuya Ohara, and Todashi Yoshino
  • Organizer: 66^<th> Annual meeting of the Japanese Cancer association
  • Place of Presentation: Yokohma, Japan
• [Presentation] Assciation of aberrant DNA methylation with linicopthoogic characteristics in Adult T cell leukemia/lymphoma (ATLL) (2007)
  • Author(s): Hiaki Sato, Takashi Oka, Yoko Shinnou, Kana Washio, Masayuki Takano, Nobuya Ohara, Mamoru Ouchia, Koichi hshima, Kenji Shimiz, Mitsne Tanimoto, Kiyoshi Takahashi, Atae Utsunomiya Tadashi Yoshino
  • Organizer: 66^<th> Annual meeting of the Japanese Cancer association
  • Place of Presentation: Yokohma, Japan
• [Presentation] Genes specifically changing DNA methylation during osteoblastic/adipocytic differentiations in mesenchymal stem cells (2007)
  • Author(s): Masayuki Takano, Takashi Oka, Yoko Shinnou, Takami Kondo Hiaki Sato, Kana Washio, Ichiro Murakai, Nobuya Ohara, adashYoshino
  • Organizer: 66th Annual meeting of the JapCancer association
  • Place of Presentation: Yokohma, Japan
• [Presentation] Molecular Pathological examination on aberrant expression of cyclinD1 and CD79a in multiple myeloma cell lines (2007)
  • Author(s): Takata K., Oka T., Tanaka T., Sato H., Murakami I., Morito T., Takano M., Washio K., Otsuki T., and Yoshino T
  • Organizer: 6th Annual meetin of the Japanese Cancer association
  • Place of Presentation: Yokohma, Japan
• [Presentation] 成人T細胞白血病/リンパ腫(ATLL)における特異的DNAメチル化と病態・臨床症状との相関 (2007)
  • Author(s): 佐藤妃映、岡剛史、近藤孝美、高野正幸、神農陽子、鷲尾佳奈、高田尚良、守都敏晃、大原信哉,大内田守、大島孝一、谷本光音、宇都宮與、高橋聖之、吉野正
  • Organizer: 第47回日本リンパ網内系学会総会
  • Place of Presentation: 淡路
• [Presentation] 胃原発悪性リンパ腫の発症・進展と特異的遺伝子のepigeneticな変化に関する検討 (2007)
  • Author(s): 近藤孝美、岡剛史、神農陽子、佐藤妃映、鷲尾佳奈、高野正幸、高田尚良、守都敏晃、大原信哉、大内田守、吉野正
  • Organizer: 第47回日本リンパ網内系学会総会
  • Place of Presentation: 淡路
• [Presentation] EPIGENETICALLY DISTINST MALIGNANT CELL POLULATION FORMS LYMPHOMA-INVOLVING LESION IN ACUTE TYPE ADULT T-CELL LEUKEMIA/LYMPHOMA (ATLL) (2007)
  • Author(s): Takashi Oka, Hiaki Sato, Yoko Nakatani, Takami Kondo, Kana Washio, Masayuki Takano, Ichiro Murakami, Nobuya Ohara , Mamoru Ouchida, Koichi Ohshima, Kenji Shiu, Mitsune animoto, Kiyoshi Takahhi, Atae Utsunomiya, Tadashi Yoshino
  • Organizer: 13th International Coference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] ABERRANT DNA METHYLATIONIS ASSOCIATD WITH THE CLINICOPATHOLOGIC CHARACTERISTICS IN PATIENTS WITH ADUL T-CELL LENKEMIA/LYMPHOMA(ATLL) (2007)
  • Author(s): Hiaki Sato, Takashi Oka, Yoko Nakatani, Takami Kondo, Kana Washio, Masayuki Takano, Ichiro Murakami, Nobuya Ohara , Mamoru Ouchida, Koichi Ohshima, Kenji Shimizu, Mitsune Tanimoto, Kiyoshi Takahashi, Atae Utsunomiya, Tadashi Yoshino
  • Organizer: 13th International Coference on Human Retrovirology HTLV and Rted Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] CPG SLAND METHYLATOR PHENOTYPE (CIMP) PROMOTES THE PROGRESSION OF ADULT LEUKEMIA/LYMPHOMA(ATLL) (2007)
  • Author(s): Hiaki Sato Takashi Oka Yoko Nakatani Takami Kondo Kana Washio Masayuki Takano Nobuya Ohara Mamoru Ouchida KoicOshima Kenjhimizu Mitsune Tanimoto Khi TakahaAtae Utsunomiya Tadhi Yoshino
  • Organizer: 13th International Conference on Human Retrovirology HTVL and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] EPIGENETICALLY DISTINST MALIGNANT CELL POLULATION FORMS LYMPHOMA-INVOLVING LESION IN ACUTE TYPE ADULT T-CELL LEUKEMIA/LYMPHOMA (ATLL). (2007)
  • Author(s): Takashi Oka1), Hiaki Sato1, 5), Yoko Nakatani1), Takami Kondo1), Kana Washio1), Masayuki Takano1), Ichiro Murakami7), Nobuya Ohara 1), Mamoru Ouchida2), Koichi Ohshima3), Kenji Shimizu2), Mitsune Tanimoto4), Kiyoshi Takahashi5), Atae Utsunomiya6), Tadashi Yoshino1)
  • Organizer: 13th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] ABERRANT DNA METHYLATION IS ASSOCIATED WITH THE CLINICOPATHOLOGIC CHARACTERISTICS IN PATIENTS WITH ADULT T-CELL LEUKEMIA/LYMPHOMA (ATLL). (2007)
  • Author(s): Hiaki Sato1, 5), Takashi Oka1), Yoko Nakatani1), Takami Kondo1), Kana Washio1), Masayuki Takano1), Ichiro Murakami7), Nobuya Ohara 1), Mamoru Ouchida2), Koichi Ohshima3), Kenji Shimizu2), Mitsune Tanimoto4), Kiyoshi Takahashi5), Atae Utsunomiya6), Tadashi Yoshino1)
  • Organizer: 13th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] CPG ISLAND METHYLATOR PHENOTYPE (CIMP) PROMOTES THE PROGRESSION OF ADULT T-CELL LEUKEMIA/LYMPHOMA (ATLL). (2007)
  • Author(s): Hiaki Sato1, 5) Takashi Oka1) Yoko Nakatani1) Takami Kondo1) Kana Washio1) Masayuki Takano1) Nobuya Ohara 1) Mamoru Ouchida2) Koichi Oshima3) Kenji Shimizu2) Mitsune Tanimoto4) Kiyoshi Takahashi5) Atae Utsunomiya6) Tadashi Yoshino1)
  • Organizer: 13th International Conference on Human Retrovirology HTLV and Related Viruses
  • Place of Presentation: Hakone, Japan
• [Presentation] Immunohistochemical analyses of PTPN6 (SHP1) on Langerhans cell histiocytosis. (2007)
  • Author(s): Ichiro Murakami, Takashi Oka Hiaki Sato, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinnou1), Kana Washio1), Masayuki Takano1), Nobuya Ohara1), and Tadashi Yoshino
  • Organizer: 66thAnnual meeeting of the Japanese Cancer association
  • Place of Presentation: Yokohama, Japan
• [Presentation] Association of aberrant DNA methylation with clinicopahthologic characteristics in Adult T cell leukemia/lymphoma (ATLL). (2007)
  • Author(s): Hiaki Sato1), Takashi Oka1), Yoko Shinnou1), Kana Washio1), Masayuki Takano1), Nobuya Ohara1), Mamoru Ouchida2), Koichi Ohshima4), Kenji Shimizu2), Mitsune Tanimoto3), Kiyoshi Takahashi1), Atae Utsunomiya5), Tadashi Yoshino1)
  • Organizer: 66thAnnual meeeting of the Japanese Cancer association
  • Place of Presentation: Yokohama, Japan
• [Presentation] Genes specifically changing DNA methylation during osteoblastic/adipocytic differentiations in mesenchymal stem cells (2007)
  • Author(s): Masayuki Takano1, Takashi Oka1, Yoko Shinnou1, Takami Kondo1, Hiaki Sato1, 2, Kana Washio1, Ichiro Murakami3, Nobuya Ohara1, Tadashi Yoshino1
  • Organizer: 66thAnnual meeeting of the Japanese Cancer association
  • Place of Presentation: Yokohama, Japan
• [Patent(Industrial Property Rights)] 成人T細胞白血病・リンパ腫 (ATLL)の予後推定法及びキャト (2008)
  • Inventor(s): 岡剛史、佐藤妃映、大内田守、吉野正、
  • Industrial Property Rights Holder: 岡山大学
  • Industrial Property Number: 2008-071783
  • Filing Date: 2008-03-19