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Characteristics of leukemic niche with regard to Mediator transcriptional coregulatory complex

Research Project

Project/Area Number 17K09012
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionKobe University

Principal Investigator

Ito Mitsuhiro  神戸大学, 保健学研究科, 教授 (50362794)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMED1 / 造血ニッチ / MGP / 白血病幹細胞 / メディエーター / Gla化 / 転写コアクチベーター / ビタミンD受容体 / 生体分子 / 生理活性 / 内科 / 発現制御
Outline of Final Research Achievements

Transcription, the mechanism of RNA synthesis from DNA as a template, is dictated by Mediator transcriptional coregulatory complex. The MED1 component of Mediator complex is necessary for appropriate hematopoiesis. In this study, MGP produced by bone marrow stromal cells through MED1 was thought to employ a physiological role in this mechanism. MGP was found to support not only normal, but also malignant, hematopoietic progenitor cells. Thus MGP was proven to be a novel niche factor in hematopoiesis, which, as the first proposal of MGP’s role in hematopoiesis, signifies this study.

Academic Significance and Societal Importance of the Research Achievements

白血病は血液がんであり、抗がん剤治療や骨髄移植等で予後の改善が得られてはいるが、今なお死の転機をとげること多く、また治療もつらい抗がん剤の治療が主体になるものが多い。これらを改善するには新たなアプローチが必要であり、そのためには白血病のみならず正常の造血機構を知る必要がある。本研究で、MGPが造血の支持機構を担うことが初めて証明された。また、正常造血と悪性造血における違いも明らかになった。本研究の先に、MGPを標的とする治療アプローチがありうることを示すものであり、今後の研究の動向に期待したい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (41 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (23 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] ロックフェラー大学(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] The Rockefeller University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ロックフェラー大学(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] 台湾国立大学(台湾)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Detection of a novel CBFB-MYH11 fusion transcript in acute myeloid leukemia M1 with inv(16)(p13q22).2020

    • Author(s)
      Kurata K, Yamamoto K, Okazaki Y, Noguchi Y, Matsui K, Matsumoto H, Inui Y, Yakushijin K, Ito M, Nakamachi Y, Matsuoka H, Saegusa J, Minami H.
    • Journal Title

      Cancer Genet

      Volume: 241 Pages: 72-76

    • DOI

      10.1016/j.cancergen.2019.07.005

    • NAID

      120006818788

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MYC amplification on double minute chromosomes in plasma cell leukemia with double IGH/CCND1 fusion genes.2020

    • Author(s)
      Yamamoto K, Yakushijin K, Ito M, Goto H, Higashime A, Kajimoto K, Hayashi Y, Matsuoka H, Minami H
    • Journal Title

      Cancer Genet

      Volume: 242 Pages: 35-40

    • DOI

      10.1016/j.cancergen.2020.01.049

    • NAID

      120006823972

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrix Gla protein maintains normal and malignant hematopoietic progenitor cells by interacting with bone morphogenetic protein-42020

    • Author(s)
      Kana Kuronuma, Aya Yokoi, Tomoya Fukuoka, Muneaki Miyata, Akio Maekawa, Satowa Tanaka, Leo Matsubara, Chie Goto, Miki Matsuo, Hao-Wei Han, Mai Tsuruta, Haruka Murata, Hikari Okamoto, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    • Journal Title

      Heliyon

      Volume: 6 Issue: 4 Pages: 03743-03743

    • DOI

      10.1016/j.heliyon.2020.e03743

    • NAID

      120006844969

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Successful Bridging Chemotherapy with Gemcitabine, Carboplatin, and Dexamethasone before Unrelated Stem Cell Transplantation for Hepatosplenic T-cell Lymphoma2019

    • Author(s)
      Okuni M、Yakushijin K、Uehara K、Ichikawa H、Suto H、Hashimoto A、Tanaka Y、Shinzato I、Sakai R、Mizutani Y、Nagao Si、Kurata K、Kakiuchi S、Miyata Y、Inui Y、Saito Y、Kawamoto S、Yamamoto K、Ito M、Matsuoka H、Minami H
    • Journal Title

      Internal Medicine

      Volume: 58 Issue: 5 Pages: 707-712

    • DOI

      10.2169/internalmedicine.1266-18

    • NAID

      130007606906

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2019-03-01
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PML-RARα Induces All-Trans Retinoic Acid-Dependent Transcriptional Activation Through Interaction With MED12019

    • Author(s)
      Tomoya Fukuoka, Asami Kawai, Taku Takahara, Mahiro Mori, Robert G Roeder, Natsumi Hasegawa, Mitsuhiro Ito
    • Journal Title

      Transcription

      Volume: 10 Issue: 3 Pages: 147-156

    • DOI

      10.1080/21541264.2019.1624467

    • NAID

      120006653243

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Translin restricts the growth of pubertal mammary epithelial cells estrogen-independently in mice.2019

    • Author(s)
      Matsubara L, Fukuoka T, Sudo K, Fukunaga T, Imanishi A, Kuronuma K, Matsuo M, Kamoshida S, Hasegawa N, Asano S, Ito M.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 521 Issue: 3 Pages: 562-568

    • DOI

      10.1016/j.bbrc.2019.10.176

    • NAID

      120006784500

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human herpesvirus 6 encephalitis in patients administered mycophenolate mofetil as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation2018

    • Author(s)
      Inui Y、Yakushijin K、Okamura A、Tanaka Y、Shinzato I、Nomura T、Ichikawa H、Mizutani Y、Kitao A、Kurata K、Kakiuchi S、Miyata Y、Sanada Y、Kitagawa K、Uryu K、Kawamoto S、Yamamoto K、Matsuoka H、Murayama T、Ito M、Minami H
    • Journal Title

      Transplant Infectious Disease

      Volume: 21 Issue: 1

    • DOI

      10.1111/tid.13024

    • NAID

      120006888556

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Translin modulates mesenchymal cell proliferation and differentiation in mice2018

    • Author(s)
      Ikeuchi Yukiko、Imanishi Azusa、Sudo Katsuko、Fukunaga Takako、Yokoi Aya、Matsubara Leo、Goto Chie、Fukuoka Tomoya、Kuronuma Kana、Kono Ruri、Hasegawa Natsumi、Asano Shigetaka、Ito Mitsuhiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 504 Issue: 1 Pages: 115-122

    • DOI

      10.1016/j.bbrc.2018.08.141

    • NAID

      120006533204

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Invasive Scopulariopsis alboflavescens infection in patient with acute myeloid leukemia2018

    • Author(s)
      Kurata Keiji、Nishimura Sho、Ichikawa Hiroya、Sakai Rina、Mizutani Yu、Takenaka Kei、Kakiuchi Seiji、Miyata Yoshiharu、Kitao Akihito、Yakushijin Kimikazu、Kawamoto Shinichiro、Yamamoto Katsuya、Ito Mitsuhiro、Matsuoka Hiroshi、Tokimatsu Issei、Kamei Katsuhiko、Minami Hironobu
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 6 Pages: 658-664

    • DOI

      10.1007/s12185-018-2496-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of Oral Ruxolitinib in a Patient with Refractory Chronic Spontaneous Urticaria2018

    • Author(s)
      Fukunaga A、Ito M、Nishigori C
    • Journal Title

      Acta Dermato Venereologica

      Volume: 98 Issue: 9 Pages: 904-905

    • DOI

      10.2340/00015555-3006

    • NAID

      120006536964

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early lymphocyte recovery predicts clinical outcome after HSCT with mycophenolate mofetil prophylaxis in the Japanese population.2018

    • Author(s)
      Kurata K, Yakushijin K, Mizuno I, Gomyo H, Okamura A, Ichikawa H, Sakai R, Mizutani Y, Kakiuchi S, Miyata Y, Kitao A, Sanada Y, Inui Y, Uryu K, Kawamoto S, Sugimoto T, Yamamoto K, Ito M, Matsuoka H, Murayama T, Minami H
    • Journal Title

      Int J Hematol

      Volume: 印刷中 Issue: 1 Pages: 58-65

    • DOI

      10.1007/s12185-018-2437-z

    • NAID

      120006621159

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Case of Classical Hodgkin Lymphoma with Total Lymph Node Infarction2018

    • Author(s)
      Okuni M, Yakushijin K, Sakai Y, Suto H, Ichikawa H, Sakai R, Kakiuchi S, Kurata K, Mizutani Y, Kitao A, Miyata Y, Saito Y, Kawamoto S, Yamamoto K, Ito M, Matsuoka H, Minami H.
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 58 Issue: 1 Pages: 24-26

    • DOI

      10.3960/jslrt.17026

    • NAID

      130006512991

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Solitary plasmacytoma with unicentric Castleman disease in a 16-year-old patient.2019

    • Author(s)
      Yoko Ishikawa,Keiji Kurata,Kimikazu Yakushijin, Katsuya Yamamoto,Mitsuhiro Ito,Hiroshi Matsuoka,Hitomi Hara, Hikaru Kubota,Daisuke Miyawaki,Toshinori Soejima,Ryohei Sasaki,Tomoo Ito,Hironobu Minami.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The interaction of PML-RARα with MED1 initiates ATRA dependent transcriptional activation.2019

    • Author(s)
      Tomoya Fukuoka,Miki Matsuo,Hikaru Tsutsumi,Mana Morikawa, Rino Kishida,Manami Tsuji,Kyo Saiki,Naoya Kanada, Mizuha Anamoto,Natsumi Hasegawa,Mitsuhiro Ito
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MGP supports niche-dependent myeloid leukemic cells in a Glu γ-carboxylation independent manner.2019

    • Author(s)
      Haruka Murata,Kana Kuronuma,Leo Matsubara,Aya Yokoi, Hikari Okamoto,Mai Tsuruta,Tomoya Fukuoka,Miki Matsuo, Natsumi Hasegawa,Shigetaka Asano,Mitsuhiro Ito
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ATRA dependent interaction of MED1 with oncofusion protein PML-RARα initiates transcriptional activation2019

    • Author(s)
      Tomoya Fukuoka, Miki Matsuo, Hikaru Tsutsumi, Rino Kishida, Manami Tsuji, Mana Morikawa, Mizuha Anamoto, Naoya Kanada, Kyo Saiki, Robert G. Roeder, Natsumi Hasegawa, Mitsuhiro Ito
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Matrix Gla protein is a niche factor that supports myeloid leukemic cells without Glu γ-carboxylation.2019

    • Author(s)
      Mai Tsuruta, Kana Kuronuma, Leo Matsubara, Haruka Murata, Hikari Okamoto, Hao-Wei Han, Tomoya Fukuoka, Miki Matsuo, Shun Ito, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Translin modulates mesenchymal cell proliferation and differentiation in mice2019

    • Author(s)
      Kana Kuronuma, Yukiko Ikeuchi, Azusa Imanishi, Katsuko Sudo, Takako Fukunaga, Leo Matsubara, Aya Yokoi, Chie Goto, Tomoya Fukuoka, Miki Matsuo, Ruri Kono, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MGP interacts with BMP-4 and BMP-2 and supports normal and malignant hematopoietic stem/progenitor cells2018

    • Author(s)
      Aya Yokoi, Kana Kuronuma, Tomoya Fukuoka, Chie Goto, Miki Matsuo, Eri Adachi, Naoko Okada, Hikaru Tsutsumi, Mirano Kajitani, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      60th Annual Meeting of the American Society of Hematology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mediator transcriptional coregulatory complex interacts with GATA1 at its N-terminal activation domain2018

    • Author(s)
      Miki Matsuo, Tomoya Fukuoka, Hikaru Tsutsumi, Eri Adachi, Kie Hirano, Erika Haruna, Rino Kishida, Manami Tsuji, Tomomi Hisatsune, Natsumi Hasegawa, Mitsuhiro Ito
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] CCL5は造血ニッチモデルにおいて白血病幹細胞の増殖を特異的に抑制する2018

    • Author(s)
      後藤千恵、横井彩、黒沼加奈、岡田尚子、梶谷未来野、松原怜央、長谷川菜摘、浅野茂隆、伊藤光宏
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Role for MED1 in induction of group 2 innate lymphoid cells in visceral adipose tissue2018

    • Author(s)
      Eri Adachi, Kie Hirano, Chie Goto, Aya Yokoi, Kana Kuronuma, Erika Haruna, Rino Kishida, Robert G. Roeder, Natsumi Hasegawa, Tomoya Fukuoka, Mitsuhiro Ito
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] MGP interacts with BMP-4 and supports normal and malignant hematopoietic stem/progenitor cells2018

    • Author(s)
      Kana Kuronuma, Aya Yokoi, Tomoya Fukuoka, Chie Goto, Eri Adachi, Miki Matsuo, Hikaru Tsutsumi, Naoko Okada, Mirano Kajitani, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mediator transcriptional coregulatory complex interacts with GATA1 N-terminal activation domain2018

    • Author(s)
      Miki Matsuo, Tomoya Fukuoka, Hikaru Tsutsumi, Kie Hirano, Manami Tsuji, Tomomi Hisatsune, Robert G. Roeder, Natsumi Hasegawa, Mitsuhiro Ito
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 自家末梢血幹細胞移植における栄養状態と予後に関する後方視的解析2018

    • Author(s)
      水谷優、藥師神公和、市川大哉、坂井里奈、後藤秀彰、倉田啓史、西村明子、北尾章人、田淵聡子、瓜生恭章、垣内誠司、宮田吉晴、乾由美子、眞田幸尚、今村善宜、船越洋平、高橋路子、岡村篤夫、川本晋一郎、山本克也、伊藤光宏、松岡広、南博信
    • Organizer
      第40回日本造血移植学会総会、ロイトン札幌
    • Related Report
      2017 Research-status Report
  • [Presentation] 非血縁者間骨髄移植前の病勢コントロールとしてGCD療法が有効であった肝脾原発T細胞リンパ腫の一例2018

    • Author(s)
      大國まりか、市川大哉、須藤洋崇、橋本朗子、田中康博、新里偉咲、長尾茂樹、坂井里奈、水谷優、北尾章人、倉田啓史、垣内誠司、宮田吉晴、乾由美子、斎藤泰之、藥師神公和、川本晋一郎、伊藤光宏、山本克也、松岡広、南博信
    • Organizer
      第40回日本造血移植学会総会、ロイトン札幌
    • Related Report
      2017 Research-status Report
  • [Presentation] 全自動尿中有形成分分析装置 UF-5000 の性能評価2017

    • Author(s)
      牧 亜矢子、金山 敦子、井地 陽子、河野 江利子、池本 敏行、伊藤 光宏、岡田 仁克
    • Organizer
      第66回日本医学検査学会、幕張メッセ国際会議場
    • Related Report
      2017 Research-status Report
  • [Presentation] 全自動尿中有形成分分析装置UF-5000による尿中細菌測定の有用性2017

    • Author(s)
      牧 亜矢子、金山 敦子、河野江利子、柴田 有理子、池本 敏行、伊藤 光宏、岡田 仁克
    • Organizer
      第64回日本臨床検査医学会学術集会,国立京都国際会館
    • Related Report
      2017 Research-status Report
  • [Presentation] MGP is a novel niche factor for normal and malignant hematopoietic stem/precursor cells.2017

    • Author(s)
      Aya Yokoi, Chie Goto, Akio Maekawa, Leo Matsubara, Takako Fukunaga, Kana Kuronuma, Natsumi Hasegawa, Masamitsu Harada, Yoichi Nakao, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      第79 回日本血液学会学術集会、東京国際フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] Retrospective analysis of the ESHAP regimen for malignant lymphoma in Kobe University Hospital.2017

    • Author(s)
      Yoshiharu Miyata, Kimikazu Yakushijin, Hiroya Ichikawa, Rina Sakai, Hideaki Goto, Yu Mizutani, Keiji Kurata, Seiji Kakiuchi, Akihito Kitao, Shinichiro Kawamoto, Katsuya Yamamoto, Mitsuhiro Ito, Hiroshi Matsuoka, Hironobu Minami
    • Organizer
      第79 回日本血液学会学術集会、東京国際フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] MGP is a novel niche molecule that modulates normal and malignant hematopoietic stem/precursor cells.2017

    • Author(s)
      Aya Yokoi, Chie Goto, Kana Kuronuma, Akio Maekawa, Leo Matsubara, Takako Fukunaga, Natsumi Hasegawa, Masamitsu Harada, Shigetaka Asano, Mitsuhiro Ito
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会・第90回日本生化学会大会)、神戸国際会議場
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写共役因子MED1の核内受容体結合能は低温環境での体温維持に必須である2017

    • Author(s)
      平野希依、物延沙耶、安達枝里、長崎洋樹、福岡知也、峰松侑希、後藤千恵、横井彩、松尾美希、Robert G. Roeder、長谷川菜摘、伊藤光宏
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会・第90回日本生化学会大会)、神戸国際会議場
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写共役因子MED1によるIL-33誘導性の2型自然リンパ球の動員調節2017

    • Author(s)
      安達枝里、長谷川菜摘、前川茜、物延沙耶、平野希依、後藤千恵、横井彩、黒沼加菜、宮田宗明、高井義美、Robert G. Roeder、伊藤光宏
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会・第90回日本生化学会大会)、神戸国際会議場
    • Related Report
      2017 Research-status Report
  • [Presentation] MED1の核内受容体結合能を廃絶した変異マウスにおける脂質代謝制御分子の発現2017

    • Author(s)
      物延沙耶、平野希依、安達枝里、峰松侑希、松尾美希、後和佳澄、服部美咲、黒沼加奈、Robert G. Roeder、長谷川菜摘、伊藤光宏
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会・第90回日本生化学会大会)、神戸国際会議場
    • Related Report
      2017 Research-status Report
  • [Presentation] GATA1のN端活性化ドメインを介する転写活性化におけるメディエーターの関与の可能性2017

    • Author(s)
      福岡知也、松尾美希、後和佳澄、森真洋、河合麻美、水田駿平、峰松侑希、服部美咲、Robert G. Roeder、長谷川菜摘、伊藤光宏
    • Organizer
      2017年度生命科学系学会合同年次大会(第40回日本分子生物学会年会・第90回日本生化学会大会)、神戸国際会議場
    • Related Report
      2017 Research-status Report
  • [Book] 遺伝子発現制御機構2017

    • Author(s)
      田村 隆明、浦  聖惠他(分担執筆)
    • Total Pages
      264
    • Publisher
      東京化学同人
    • ISBN
      9784807909179
    • Related Report
      2017 Research-status Report
  • [Remarks] 神戸大学保健学研究科 血液学研究室

    • URL

      http://www2.kobe-u.ac.jp/~itomi/

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2022-02-22  

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