Development of the new myeloma treatment based on the comprehensive analysis for genome structure abnormality and epigenome abnormality

• Project/Area Number: 23591399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: ISHIDA Tadao 札幌医科大学, 医学部, 准教授 (20305220)
• Co-Investigator(Kenkyū-buntansha): IKEDA Hiroshi 札幌医科大学, 道民医療推進学講座, 助教 (60570132)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: multiple myeloma / methylation / LINE-1 / multiple mueloma / myeloma / 多発性骨髄腫 / 長鎖散在反復配列 / メチル化

Research Abstract

Global levels of the long interspersed nuclear element-1 (LINE-1) methylation declined with the degree of malignancy of plasma cells, and there was a significant inverse correlation between the degree of genomic loss and the LINE-1 methylation levels. Finally, there was a significant association between LINE-1 hypomethylation and poorer overall survival. Our findings suggest that global hypomethylation of LINE-1 may increase the malignant potential of myeloma cells by inducing broad copy-number losses.

Research Products

• [Journal Article] Multiple myeloma : chromosomal abnormalities, clinical features and prognosis (2013)
  • Author(s): Ishida T
  • Journal Title: Rinsho Ketsueki Volume: 54 Pages: 1856-66
  • NAID: 10031196331
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24064837
  • Peer Reviewed
• [Journal Article] 多発性骨髄腫におけるエピゲノム異常と治療の可能性 (2013)
  • Author(s): 安井寛、石田禎夫．
  • Journal Title: 血液内科 Volume: 66 Pages: 337-345
• [Journal Article] 多発性骨髄腫：染色体異常と臨床病型・予後 (2013)
  • Author(s): 石田禎夫．
  • Journal Title: 臨床血液 Volume: 54 Pages: 1856-1866
  • NAID: 10031196331
  • Peer Reviewed
• [Journal Article] 多発性骨髄腫の治療（2）移植非適応例 (2013)
  • Author(s): 石田禎夫
  • Journal Title: 臨床血液 Volume: 54 Pages: 711-714
  • Peer Reviewed
• [Journal Article] 多発発性骨髄腫治療におけるトリプレット療法 (2013)
  • Author(s): 石田禎夫
  • Journal Title: 日本臨床 Volume: 71 Pages: 1691-1696
• [Journal Article] 多発性骨髄腫に対する免疫調節薬治療 (2013)
  • Author(s): 石田禎夫
  • Journal Title: Jpn J Cancer Chemother Volume: 40 Pages: 589-593
• [Journal Article] 高齢者多発性骨髄腫の特徴と治療の実際 (2013)
  • Author(s): 石田禎夫
  • Journal Title: 血液フロンティア Volume: 23 Pages: 1733-1742
• [Journal Article] 移植非適応の多発性骨髄腫患者に対する治療 (2013)
  • Author(s): 石田禎夫
  • Journal Title: International Journal of Myeloma Volume: 3 Pages: 12-25
  • Peer Reviewed
• [Journal Article] 多発性骨髄腫における神経障害のマネジメント (2013)
  • Author(s): 石田禎夫
  • Journal Title: 血液内科 Volume: 66 Pages: 257-264
  • NAID: 40019614269
• [Journal Article] Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma (2012)
  • Author(s): Aoki Y,Ikeda H, Ishida T, et al
  • Journal Title: Genome Med Volume: 4
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/23259664
  • Peer Reviewed
• [Journal Article] Model of translational cancer research in multiple myeloma (2012)
  • Author(s): Yasui H, Ishida T, Maruyama R, Nojima M, Ikeda H, Suzuki H, Hayashi T, Shinomura Y, Imai K
  • Journal Title: Cancer Sci Volume: 103 Issue: 11 Pages: 1907-1912
  • DOI: 10.1111/j.1349-7006.2012.02384.x
  • Peer Reviewed
• [Journal Article] Heat stress activates ER stress signals which suppress the heat shock response, an effect occurring preferentially in the cortex in rats (2012)
  • Author(s): Liu Y, Ukai W, Hashimoto E, et al
  • Journal Title: Mol Biol Rep Volume: 39(4) Issue: 4 Pages: 3987-3993
  • DOI: 10.1007/s11033-011-1179-2
  • Peer Reviewed
• [Journal Article] Genomic vulnerability to LINE-1 hypomethylation is a potential determinant of the clinicogenetic features of multiple myeloma. (2012)
  • Author(s): Aoki Y, Nojima M, Suzuki H, Yasui H, Maruyama R, Yamamoto E, Ashida M, ItagakiM, Asaoku H, Ikeda H, Hayashi T, Imai K, Mori M, Tokino T, Ishida T, Toyota M, Shinomura Y.
  • Journal Title: Genome Med. Volume: 4 Pages: 101-114
  • Peer Reviewed
• [Journal Article] Epidemiology and treatment outcome of invasive fungal infections in patients with hematologicalmalignancies (2012)
  • Author(s): Kurosawa M, Yonezumi M, Hashino S, Tanaka J, Nishio M, Kaneda M, Ota S, Koda K, Suzuki N, Yoshida M, Hirayama Y, Takimoto R, Torimoto Y,Mori A, Takahashi T, Iizuka S, Ishida T, Kobayashi R, Oda T, Sakai H, Yamamoto S, Takahashi F, Fukuhara T
  • Journal Title: Int J Hematol Volume: 96(6) Issue: 6 Pages: 748-57
  • DOI: 10.1007/s12185-012-1210-y
  • Peer Reviewed
• [Journal Article] t(4；14)転座と多発性骨髄腫SETドメイン蛋白質（MMSET）の意義 (2012)
  • Author(s): 石田禎夫、安井寛
  • Journal Title: 医学のあゆみ Volume: 242 Pages: 1063-1067
• [Journal Article] 多発性骨髄腫に対する治療のエビデンスレビュー～高齢者に対する初回治療～ (2012)
  • Author(s): 青木由佳、石田禎夫
  • Journal Title: 血液フロンティア Volume: 22 Pages: 661-669
• [Journal Article] 多発性骨髄腫におけるエピジェネティック異常 (2012)
  • Author(s): 石田禎夫．青木由佳
  • Journal Title: 血液内科 Volume: 64 Pages: 405-411
• [Journal Article] In vitro and in vivo antitumor effects of recombinant bispecific antibodies based on humanized anti-EGFR antibody (2011)
  • Author(s): Watanabe Y, Yasui H, et al
  • Journal Title: Oncol Rep Volume: 26(4) Pages: 949-55
  • DOI: 10.3892/or.2011.1382
  • Peer Reviewed
• [Journal Article] Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo (2011)
  • Author(s): Sasaki S., et al
  • Journal Title: PLoS One Volume: 6 Issue: 5 Pages: e19618-e19618
  • DOI: 10.1371/journal.pone.0019618
  • Peer Reviewed
• [Journal Article] Interferon-α/β and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo. (2011)
  • Author(s): Sasaki S, Ishida T, Toyota M, Ota A, Suzuki H, Takaoka A, Yasui H, Yamamoto H, Takagi H, Maeda M, Seito T,Tsujisaki M, Shinomura Y, Imai K.
  • Journal Title: PLoS One Volume: 6 Pages: 1-9
  • Peer Reviewed
• [Journal Article] Efficacy of Long-Term Treatment with Low-Dose Thalidomide for Patients with Relapsed/Refractory Multiple Myeloma. (2011)
  • Author(s): Shimizu K, Murakami H, Sawamura M, Hattori Y, Okamoto S, Miwa A,Sugiura I, Shimazaki C,Taniwaki M,Ishida T, KosugiH,Yuge M,Iida S, Ishida T,Sunami K,Asaoku H,Sakai A,Abe M,Takagi T.
  • Journal Title: International Journal of Clinical Medicine Volume: 2 Pages: 570-575
  • Peer Reviewed
• [Journal Article] In vitro and in vivo antitumor effects of recombinant bispecific antibodies based on humanized anti-EGFR antibody. (2011)
  • Author(s): Watanabe Y, Asano R, Arai K, Shimomura I, Ogata H, Kawaguchi H, Hayashi H, Ohtsuka H, Yoshida H, Katayose Y, Egawa S, Nakanishi T, Umetsu M, Ishida T, Imai K, Kudo T, Unno M, Kumagai I.
  • Journal Title: Oncol Rep. Volume: 26 Pages: 949-955
  • Peer Reviewed
• [Journal Article] 染色体ハイリスク骨髄腫に対する治療の最新知見 (2011)
  • Author(s): 石田禎夫
  • Journal Title: 血液フロンティア Volume: 21 Pages: 63-71
• [Journal Article] Thalidomideの薬剤特性、治療成績、有害反応 (2011)
  • Author(s): 石田禎夫、青木由佳
  • Journal Title: 内科 Volume: 108 Pages: 261-267
• [Presentation] 多発性骨髄腫:染色体異常と臨床病型・予後 (2013)
  • Author(s): 石田禎夫
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌, (教育講演)
• [Presentation] 染色体異常と臨床病型・予後 (2013)
  • Author(s): 石田禎夫
  • Organizer: 第75回日本血液学会学術集会．教育講演
  • Place of Presentation: 札幌
  • Invited
• [Presentation] Hypomethylation of endogenous retrotransposons is correlated with frequent chromosomal deletions and poor prognosis in multiple myeloma (2012)
  • Author(s): Yasui H, Ishida T, et al
  • Organizer: 17th Congress of the European Hematology Association
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2012-06-15
• [Presentation] Hypomethylation of Retrotransposons is Correlated with Malignant Levels, Frequency of Chromosomal Aberrations, and Poor Prognosis in Multiple Myeloma (2012)
  • Author(s): Yasui H, Ishida T, et al
  • Organizer: JSH International Symposium 2012 in Kawagoe
  • Place of Presentation: Kawagoe, Japan
• [Presentation] Hypomethylation of Retrotransposons is Correlated with Malignant Levels, Frequency of Chromosomal Aberrations, and Poor Prognosis in Multiple Myeloma. (2012)
  • Author(s): Yasui H, Aoki Y, Nojima M, Suzuki H, Maruyama Y, Maruyama R, Yamamoto E, Itagaki M, Ikeda H, Hayashi T, Asaoku H, Imai K, Ishida T, Shinomura Y.
  • Organizer: JSH International Symposium 2012 in Kawagoe
  • Place of Presentation: Kawagoe, Japan
• [Presentation] Hypomethylation of endogenous retrotransposons is correlated with frequent chromosomal deletions and poor prognosis in multiple myeloma. (2012)
  • Author(s): Yasui H, Aoki Y, Nojima M, Suzuki H, Maruyama Y, Maruyama R, Yamamoto E, Itagaki M, Ikeda H, Hayashi T, Asaoku H, Imai K, Ishida T, Shinomura Y.
  • Organizer: 17th Congress of the European Hematology Association
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] 多発性骨髄腫の発生におけるDNAメチロームの意義：MBDシーケンシング法によるアプローチ (2012)
  • Author(s): Nojima M, Aoki Y, Yasui H, Maruyama R, Asaoku H, Ishida T, Tokino T, Mori M, Suzuki H, Shinomura Y.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: Sapporo, Japan
• [Presentation] 多発性骨髄腫における骨髄ストローマ細胞と単球との相互作用の解析 (2012)
  • Author(s): Ikeda H, Aoki Y, Yasui H, Hayashi T, Ishida T, Sasaki Y, Shinomura Y.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: Sapporo, Japan
• [Presentation] The significance of global hypomethylation of DNA repetitive elements in multiple myeloma (2012)
  • Author(s): Aoki Y, Nojima M, Yasui H, Suzuki H, Maruyama R, Ikeda H, Hayashi T, Ishida T, Asaoku H, Shinomura Y.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: Kyoto, Japan
• [Presentation] Genomic screening for genes silenced by DNA methylation explore epigenetic biomarkers for prediction of sensitivity to dexamethasone in MM (2011)
  • Author(s): Ishida T, et al
  • Organizer: 13^<th> International Myeloma Workshop
  • Place of Presentation: Paris, France
  • Year and Date: 2011-05-03
• [Presentation] GENOMIC SCREENING FOR GENES SILENCED BY DNA METHYLATION TO EXPLORE EPIGENETIC BIOMARKERS FOR PREDICTION OF SENSITIVITY TO DEXAMETHASONE IN MULTIPLE MYELOMA (2011)
  • Author(s): ISHIDA T, YASUI H, NOJIMA M, AOKI Y, ITAGAKI M, MARUYAMA R, IKEDA H, SUZUKI H, SAKAI H, HAYASHI T, ASAOKU H, IMAI K, TOYOTA M, SHINOMURA Y
  • Organizer: IMW
  • Place of Presentation: Paris
• [Presentation] The relationship between DNA hypomethylation of repetitive elements and (2011)
  • Author(s): Yuka Aoki, Masanori Nojima,Hiroshi Yasui, Hiromu Suzuki,Reo Maruyama, Tadao Ishida, Hideki Asaoku, Takashi Tokino,Minoru Toyota, Yasuhisa Shinomura
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋
• [Presentation] Methylome analysis using next-generation sequencing in multiple myeloma (2011)
  • Author(s): Hiroshi Yasui, Masanori Nojima, Yuka Aoki,Shintaro Takatsuka, Reo Maruyama, Hiromu Suzuki, Toshiaki Hayashi, Hideki Asaoku, Kohzoh Imai,Minoru Toyota, Tadao Ishida, Yasuhisa Shinomura
  • Organizer: 日本血液学会
  • Place of Presentation: 名古屋
• [Book] Triplets therapy for the patients of multiple myeloma (2013)
  • Author(s): Ishida T
  • Publisher: Nihon Rinsho
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24205736
• [Book] Myeloma therapy(2) Treatment of transplant-ineligible patients (2013)
  • Author(s): Ishida T
  • Publisher: Rinsho Ketsueki
• [Book] 多発性骨髄腫に対する初期治療の概念.多発性骨髄腫Updating第3巻 (2013)
  • Author(s): 石田禎夫, (編集清水一之、阿部正博、島崎千尋、鈴木憲史)
  • Publisher: 医薬ジャーナル社
• [Book] 多発性骨髄腫におけるエピゲノム異常と治療の可能性 (2013)
  • Author(s): 安井寛、石田禎夫
  • Publisher: 血液内科
• [Book] 多発性骨髄腫における神経障害のマネジメント (2013)
  • Author(s): 石田禎夫
  • Publisher: 血液内科
• [Book] 移植非適応の多発性骨髄腫患者に対する治療 (2013)
  • Author(s): 石田禎夫
  • Publisher: International Journal of Myeloma
• [Book] 多発性骨髄腫に対する免疫調節薬治療 (2013)
  • Author(s): 石田禎夫
  • Publisher: Jpn J Cancer Chemother
• [Book] 高齢者多発性骨髄腫の特徴と治療の実際 (2013)
  • Author(s): 石田禎夫
  • Publisher: 血液フロンティア
• [Book] IgM型多発性骨髄腫. 新領域別症候群シリーズ No.23 (2013)
  • Author(s): 池田博、石田禎夫
  • Publisher: 日本臨床社
• [Book] 日本臨床社 (2013)
  • Author(s): 池田博、石田禎夫
  • Publisher: IgE型多発性骨髄腫. 新領域別症候群シリーズ No.23
• [Book] 骨髄腫の腎病変に対する管理、治療．多発性骨髄腫 Updating 第2巻 (2013)
  • Author(s): 石田禎夫
  • Publisher: 医薬ジャーナル社
• [Book] 多発性骨髄腫に対する初期治療の概念．多発性骨髄腫 Updating 第3巻． (2013)
  • Author(s): 石田禎夫
  • Publisher: 医薬ジャーナル社
• [Book] 自家移植の位置づけ．多発性骨髄腫 Updating 第4巻． (2013)
  • Author(s): 石田禎夫
  • Publisher: 医薬ジャーナル社
• [Book] 多発性骨髄腫 Updating 第2巻（骨髄腫の腎病変に対する管理、治療） (2013)
  • Author(s): 石田禎夫
  • Total Pages: 303
  • Publisher: 医薬ジャーナル社（大阪）
• [Book] 発症機構とエピジェティックス異常6)多発性骨髄腫.造血器腫瘍とエピジェティクス-治療への応用と新たな展開- (2012)
  • Author(s): 安井寛,石田禎夫, (木崎昌弘編)
  • Publisher: 医薬ジャーナル社
• [Book] 多発性骨髄腫-現状と進歩検査法と病態t(4;14)転座と多発性骨髄腫SETドメイン蛋白質(MMSET)の意 (2012)
  • Author(s): 石田禎夫、安井寛
  • Publisher: 医学のあゆみ
• [Book] 多発性骨髄腫におけるエピジェネティック異常 (2012)
  • Author(s): 石田禎夫.青木由佳
  • Publisher: 血液内科
• [Book] 多発性骨髄腫に対する治療のエビデンスレビュー～高齢者に対する初回治療～ (2012)
  • Author(s): 青木由佳、石田禎夫
  • Publisher: 血液フロンティア
• [Book] 多発性骨髄腫治療マニュアル （多発性骨髄腫における新規治療薬の有害事象対策） (2012)
  • Author(s): 石田禎夫
  • Total Pages: 316
  • Publisher: 南江堂（東京）
• [Book] 造血器腫瘍とエピジェティクス-治療への応用と新たな展開-（多発性骨髄腫） (2012)
  • Author(s): 安井 寛, 石田禎夫
  • Total Pages: 251
  • Publisher: 医薬ジャーナル社（大阪）
• [Book] 染色体ハイリスク骨髄腫に対する治療の最新知見 (2011)
  • Author(s): 石田禎夫
  • Publisher: 血液フロンティア
• [Book] Thalidomideの薬剤特性、治療成績、有害反応 (2011)
  • Author(s): 石田禎夫、青木由佳
  • Publisher: 内科