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Lymphomagenesis pathway consisting of various cooperative genes and their relevance as molecular target therapy

Research Project

Project/Area Number 24390249
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Hematology
Research InstitutionKurume University (2014)
Aichi Cancer Center Research Institute (2012-2013)

Principal Investigator

SETO Masao  久留米大学, 医学部, 客員教授 (80154665)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsリンパ腫 / 染色体転座 / 転座関連遺伝子 / シグナルトランスダクション / MYC、BCL2 、CCND1 / 腫瘍化機構 / リンパ腫モデル / 分子標的 / 悪性リンパ腫 / ゲノム異常
Outline of Final Research Achievements

Various genetic alterations have been reported in lymphoid malignancies. Frequencies of such alterations in each disease entity are low except for translocation-juncture genes. It is not an easy task to provide evidences that such genes are directly involved in lymphomagenesis. Transgenic and know-out mouse technology is limited in analyzing several genes within a relatively short period of time. In this research project, we have established the cell culture system, using feeder cells and cytokines, which can analyze several genes by retroviral vector transduction. Indeed, we could transform normal mouse B-cells to lethally malignant lymphoma by three translocation juncture genes, MYC, BCL2 and CCND1. This system could be extended to examine oncogenic ability for several other genes reported by genomic or exome sequencing. This system will further provide a good system to screen molecular targets.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (47 results)

All 2015 2014 2013 2012 Other

All Journal Article (26 results) (of which Peer Reviewed: 25 results,  Open Access: 6 results,  Acknowledgement Compliant: 6 results) Presentation (21 results) (of which Invited: 2 results)

  • [Journal Article] Recent advances in the treatment of adult t-cell leukemia- lymphomas.2015

    • Author(s)
      Utsunomiya A, Choi I, Chihara D, Seto M.
    • Journal Title

      Cancer Sci

      Volume: 106 Issue: 4 Pages: 344-351

    • DOI

      10.1111/cas.12617

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways.2014

    • Author(s)
      Kato H, Karube K, Yamamoto K, Takizawa J, Tsuzuki S, Yatabe Y, Kanda T, Katayama M, Ozawa Y, Ishitsuka K, Okamoto M, Kinoshita T, Ohshima K, Nakamura S, Morishima Y, Seto M.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 5 Pages: 537-544

    • DOI

      10.1111/cas.12389

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.2014

    • Author(s)
      Suguro M, Yoshida N, Umino A, Kato H, Tagawa H, Nakagawa M, Fukuhara N, Karnan S, Takeuchi I, Hocking TD, Arita K, Karube K, Tsuzuki S, Nakamura S, Kinoshita T, Seto M.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 7 Pages: 897-904

    • DOI

      10.1111/cas.12442

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Array-comparative genomic hybridization profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alterations.2014

    • Author(s)
      Guo Y, Takeuchi I, Karnan S, Miyata T, Ohshima K, Seto M.
    • Journal Title

      Cancer Sci.

      Volume: 105 Issue: 4 Pages: 481-489

    • DOI

      10.1111/cas.12378

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Synergy of Myc, cell cycle regulators and the Akt pathway in the development of aggressive B-cell lymphoma in a mouse model.2014

    • Author(s)
      Arita K, Tsuzuki S, Ohshima K, Sugiyama T, Seto M.
    • Journal Title

      Leukemia

      Volume: 28 Issue: 11 Pages: 2270-2272

    • DOI

      10.1038/leu.2014.224

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular Characterization of Chronic-type Adult T-cell Leukemia/Lymphoma2014

    • Author(s)
      Yoshida N, Karube K, Utsunimiya A, Tsukasaki K, Imaizumi Y, Taira N, Uike N, Umino A, Arita K, Suguro M, Tsuzuki S, Kinoshita T, Ohshima K, Seto M.
    • Journal Title

      Cancer Research

      Volume: 74 Issue: 21 Pages: 6129-6138

    • DOI

      10.1158/0008-5472.can-14-0643

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Array CGH profiling of immunohistochemical subgroups of diffuse large B-cell lymphoma shows distinct genomic alteration.2014

    • Author(s)
      Guo Y, Takeuchi I, Karnan S, Miyata T, Ohshima K, Seto M.
    • Journal Title

      Cancer Sci.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling of Epstein-Barr virus positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways.2014

    • Author(s)
      Kato H, Karube K, Yamamoto K, Takizawa J, Tsuzuki S, Yatabe Y, Kanda T, Katayama M, Ozawa Y, Ishitsuka K, Okamoto M, Kinoshita T, Ohshima K, Nakamura S, Morishima Y, Seto M.
    • Journal Title

      Cancer Sci.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TEL(ETV6)-AML1(RUNX1) Initiates Self-renewing Fetal Pro-B Cells in Association with a Transcriptional Program Shared with Embryonic Stem Cells in Mice.2013

    • Author(s)
      Tsuzuki S and Seto M.
    • Journal Title

      Stem Cells

      Volume: 31 Issue: 2 Pages: 236-247

    • DOI

      10.1002/stem.1277

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin D1-negative mantle cell lymphoma.2013

    • Author(s)
      Seto M.
    • Journal Title

      Blood

      Volume: 121 Issue: 8 Pages: 1249-1250

    • DOI

      10.1182/blood-2013-01-475954

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of mouse models of lymphoid neoplasm using retroviral gene transduction of in vitro-induced germinal center B and T cells.2013

    • Author(s)
      Arita K, Maeda-Kasugai Y, Ohshima K, Tsuzuki S, Suguro-Katayama M, Karube K, Yoshida N, Sugiyama T, Seto M.
    • Journal Title

      Exp Hematol

      Volume: 41 Issue: 8 Pages: 731-741

    • DOI

      10.1016/j.exphem.2013.04.001

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functionally Deregulated AML1/RUNX1 Cooperates with BCR-ABL to Induce a Blastic Phase-Like Phenotype of Chronic Myelogenous Leukemia in Mice.2013

    • Author(s)
      Kiyoko Yamamoto, Shinobu Tsuzuki, Yosuke Minami, Yukiya Yamamoto, Akihiro Abe, Koichi Ohshima, Masao Seto, Tomoki Naoe.
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 9 Pages: e74864-e74864

    • DOI

      10.1371/journal.pone.0074864

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] XV. Malignant lymphoma as a consequence of clonal evolution.2013

    • Author(s)
      Seto M.
    • Journal Title

      Hematol Oncol.

      Volume: 1 Issue: S1 Pages: 84-88

    • DOI

      10.1002/hon.2073

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Clonal heterogeneity of mantle cell lymphoma revealed by array comparative genomic hybridization2013

    • Author(s)
      Fang Liu
    • Journal Title

      European Journal of Haematology

      Volume: 90 Issue: 1 Pages: 51-58

    • DOI

      10.1111/ejh.12030

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Array CGH Reveals Clonal Evolution of Adult T-Cell Leukemia/Lymphoma.2013

    • Author(s)
      Umino A
    • Journal Title

      Methods Mol Biol.

      Volume: 973 Pages: 189-196

    • DOI

      10.1007/978-1-62703-281-0_12

    • ISBN
      9781627032803, 9781627032810
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic profiling of oral squamous cell carcinomaby array-based comparative genomic hybridization2013

    • Author(s)
      Yoshioka S, Tsukamoto Y, Hijiya N, Nakada C, Uchida T, Matsuura K, Takeuchi I, Seto M, Kawano K, Moriyama M
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: 56165-56165

    • DOI

      10.1371/journal.pone.0056165

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavior of bone marrow-derived cells following in vivo transplantation: differentiation into stromal cells with roles in organ maintenance.2013

    • Author(s)
      Taguchi O, Tsujimura K, Kontani K, Harada Y, Nomura S, Ikeda H, Morita A, Sugiura H, Hayashi N, Yatabe Y, Seto M, Tatematsu M, Takahashi T, Fukushima A.
    • Journal Title

      Am J Pathol

      Volume: 182(4) Issue: 4 Pages: 1255-1262

    • DOI

      10.1016/j.ajpath.2012.12.034

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive gene expression profiles of NK cell neoplasms identify vorinostat as an effective drug candidate2013

    • Author(s)
      Kennosuke Karube
    • Journal Title

      Cancer Letter

      Volume: 333 Issue: 1 Pages: 47-55

    • DOI

      10.1016/j.canlet.2012.12.022

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Primary peripheral T-cell lymphoma, not otherwise specified of the thyroid with autoimmune thyroiditis.2013

    • Author(s)
      Yoshida N, et al
    • Journal Title

      Br J Haematol.

      Volume: 161 Issue: 2 Pages: 214-223

    • DOI

      10.1111/bjh.12255

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic profiling of renal cell carcinoma in patients with end-stage renal disease2012

    • Author(s)
      Inoue T, et al
    • Journal Title

      Cancer science

      Volume: 103 Issue: 3 Pages: 569-576

    • DOI

      10.1111/j.1349-7006.2011.02176.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of functionally defined mouse hematopoietic stem and progenitor cells by a short isoform of RUNX1/AML1.2012

    • Author(s)
      Tsuzuki S and Seto M.
    • Journal Title

      Blood

      Volume: 119(3) Issue: 3 Pages: 727-735

    • DOI

      10.1182/blood-2011-06-362277

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical value of flow cytometric immunophenotypic analysis for minimal residual disease detection in autologous stem-cell products pf follicular and mantle cell lymphomas2012

    • Author(s)
      Kato H
    • Journal Title

      Leukemia

      Volume: 26 Issue: 1 Pages: 166-169

    • DOI

      10.1038/leu.2011.183

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inverse association between soy intake and non-Hodgkin lymphoma riskamong women: a case-control study in Japan.2012

    • Author(s)
      Chihara D
    • Journal Title

      Ann Oncol.

      Volume: 23 Issue: 4 Pages: 1061-1066

    • DOI

      10.1093/annonc/mdr320

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analysis of NF-kB signal pathway-related genes in ocular MALT lymphoma.2012

    • Author(s)
      Liu F
    • Journal Title

      Int J Clin Exp

      Volume: 5 Pages: 436-441

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of multiple subclones in peripheral T-cell lymphoma, not otherwise specified with genomic aberrations.2012

    • Author(s)
      Yoshida N
    • Journal Title

      Cancer Medicine

      Volume: 1 Issue: 3 Pages: 289-294

    • DOI

      10.1002/cam4.34

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lineage-specific growth inhibition of NK cell lines by FOXO3 in association with Akt activation status.2012

    • Author(s)
      Karube K, Tsuzuki S, Yoshida N, Arita K, Liu F, Kondo E, Ko YH, Ohshima K, Nakamura S, Kinoshita T, Seto M.
    • Journal Title

      Exp. Hematol.

      Volume: 40 Issue: 12 Pages: 1005-1015

    • DOI

      10.1016/j.exphem.2012.08.005

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synergy of Myc, cell cycle regulators and the Akt pathway in a mouse model of B-cell lymphoma.2014

    • Author(s)
      在田幸太郎, 都築忍, 大島孝一, 杉山敏郎, 瀬戸加大.
    • Organizer
      第76回日本血液学会総会
    • Place of Presentation
      大阪国際会議場(大阪市)
    • Year and Date
      2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] Myc、細胞周期関連遺伝子、Aktパスウェイの協調によるマウスリンパ腫モデル2014

    • Author(s)
      都築忍, 在田幸太郎, 大島孝一, 杉山敏郎, 瀬戸加大.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synergy of Myc, cell cycle regulators and the Akt pathway in a mouse model of B-cell lymphoma.2014

    • Author(s)
      Arita K, Tsuzuki S, Ohshima K, Sugiyama T, Seto M.
    • Organizer
      2014年米国血液学会リンパ腫生物学会議
    • Place of Presentation
      コロラドスプリングス(米国)
    • Year and Date
      2014-08-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] レトロウイルスによる正常B細胞への遺伝子導入を用いた成熟B細胞腫瘍マウスモデル2014

    • Author(s)
      在田幸太郎, 都築忍, 大島孝一, 杉山敏郎, 瀬戸加大.
    • Organizer
      第24回日本サイトメトリー学会学術総会
    • Place of Presentation
      関西医科大学(枚方市)
    • Year and Date
      2014-06-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] New mouse models of B-cell lymphoma using in vitro retroviral transdu2013

    • Author(s)
      Kotaro Arita
    • Organizer
      第9回日本癌学会・AACR合同会議
    • Place of Presentation
      ラハイナ(米国)
    • Year and Date
      2013-02-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identification of Multiple Subclones in Peripheral T-CeU Lymphoma, Not Otherwise Specified with Genomic Aberrations., 2012,[口演]2012

    • Author(s)
      Noriaki Yoshida
    • Organizer
      第54回米国血液学会総会
    • Place of Presentation
      アトランタ(米国)
    • Year and Date
      2012-12-10
    • Related Report
      2012 Annual Research Report
  • [Presentation] Molecular characterization of T/NK cell malignancie.2012

    • Author(s)
      瀬戸加大
    • Organizer
      第74回日本血液学会総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2012-10-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] Expansion of mouse hematpoietic stem/progenitor cells by a short isoform of RUNX1/AML1.2012

    • Author(s)
      都築忍
    • Organizer
      第74回日本血液学会総会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2012-10-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] 悪性リンパ腫の臨床病理および分子病態の解析2012

    • Author(s)
      加留部謙之輔
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] ゲノム異常陽性の末梢性T細胞性リンパ腫、非特異型におけるサブクローの存在2012

    • Author(s)
      吉田稚明
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-20
    • Related Report
      2012 Annual Research Report
  • [Presentation] マントル細胞リンパ腫のマウスモデルの作製2012

    • Author(s)
      岸本渉
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] NK細胞性腫瘍に特異的ながん抑制遺伝子であるF0X032012

    • Author(s)
      加留部謙之輔
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] CM'T.・BCにおけるAML1/RUNX1変異とBCR-ABLの協調作用2012

    • Author(s)
      都築忍
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] NK細胞性腫瘍の機能特異的がん抑制遺伝子としてのF0X032012

    • Author(s)
      瀬戸加大
    • Organizer
      第16回日本がん分子標的治療学会学術集会
    • Place of Presentation
      西日本総合展示場(北九州市)
    • Year and Date
      2012-06-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] ゲノム異常陽性PTCL, NOSにおけるサブクローンの存在2012

    • Author(s)
      吉田稚明
    • 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)
    • Year and Date
      2012-06-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] Genomic alterations in malignant lymphoma and its implication in cancer treatment.2012

    • Author(s)
      Masao Seto
    • Organizer
      The 38th Annual Meeting of Korean Cancer Association
    • Place of Presentation
      Korea (COE Seoul)
    • Year and Date
      2012-06-13
    • Related Report
      2012 Annual Research Report
  • [Presentation] Xv. Malignant Lymphoma As A Consequence Of Clonal Evolution.

    • Author(s)
      Seto M.
    • Organizer
      12th International Conference on Malignant Lymphoma
    • Place of Presentation
      Cinema Corso (Switzerland)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] リンパ腫を形成するクローン細胞の多様性は、臨床病態を反映する

    • Author(s)
      勝呂 幸,田川博之, 竹内一郎, 吉田 稚明, 在田幸太郎, 都築 忍, 瀬戸 加大
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] New mouse model of B-cell lymphoma using retrovirally transduced normal mature B-cells.

    • Author(s)
      Arita K, Tsuzuki S, Oshima K, Sugiyama T, Seto M.
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性リンパ腫発症の分子機構.

    • Author(s)
      瀬戸加大
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] New mouse B-cell lymphoma model originated from germinal center.

    • Author(s)
      Arita K, Tsuzuki S, Oshima K, Sugiyama T, Seto M.
    • Organizer
      ロイトン札幌(札幌)
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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