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Analysis of leukemogenic mechanisms by deregulated expression of histone demethylase Fbxl10

Research Project

Project/Area Number 23390252
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHiroshima University

Principal Investigator

HONDA Hiroaki  広島大学, 原爆放射線医科学研究所, 教授 (40245064)

Co-Investigator(Kenkyū-buntansha) INABA Toshiya  広島大学, 原爆放射線医科学研究所, 教授 (60281292)
UEDA Takeshi  広島大学, 原爆放射線医科学研究所, 助教 (60585149)
HONDA Zen-ichiro  お茶の水女子大学, 保健管理センター, 教授 (70238814)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywordsヒストン脱メチル化酵素 / Fbxl10 / トランスジェニックマウス / 白血病 / 造血幹細胞 / Fbx110
Research Abstract

We generated transgenic mice that overexpress Fbxl10, a histone demethylase, in hematopoietic stem cells (HSCs), and found that the mice develop leukemia at about 1 year after birth. By bone marrow transplantation, we demonstrated that the leukemia was caused by enhanced HSC-intrinsic proliferative potentials. In addition, we found that neuron specific gene 2 (Nsg2), which encodes a protein involved in intracellular transport, was overexpressed and that genes involved in oxidative phosphorylation in mitochondria were significantly up-regulated. Our findings provide novel insights in the leukemogenic mechanisms from the viewpoint of energy metabolism and intracellular transport.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 1 results) Presentation (8 results) Remarks (3 results)

  • [Journal Article] The IL-2/CD25 Axis Maintains Distinct Subsets of Chronic Myeloid Leukemia–Initiating Cells.2014

    • Author(s)
      Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T
    • Journal Title

      Blood

      Volume: 123 Pages: 2540-2549

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A long lasting puzzle for -7/7q- syndrome.2014

    • Author(s)
      Honda H, Inaba T
    • Journal Title

      Oncotarget

      Volume: 5 Pages: 7-8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function.2014

    • Author(s)
      Nagamachi A, Nakata Y, Ueda T, Yamasaki N, Ebihara Y, Tsuji K, Honda Zi, Takubo K, Suda T, Oda H, Inaba T, Honda H
    • Journal Title

      PLos One

      Volume: 9 Issue: 1 Pages: 1-10

    • DOI

      10.1371/journal.pone.0087425

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CIZ1, a p21 Cip1 /Waf1-interacting protein, functions as a tumor suppressor in vivo2013

    • Author(s)
      Nishibe R, Watanabe W, Ueda T, Yamasaki N, Koller R, Wolff L, Honda Z-i, Ohtsubo M, Honda H
    • Journal Title

      FEBS Lett

      Volume: 587 Pages: 1529-1535

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] p130Cas plays important roles in osteoclastic bone resorption2013

    • Author(s)
      Nagai Y, Osawa K, Fukushima H, Tamura Y, Aoki K, Ohya K, Yasuda H, Hikiji H, Seta Y, Seo S, Kurokawa M, Kato S, Honda H, Nakamura I, Maki K, Jimi E
    • Journal Title

      J Bone Miner Res

      Volume: 28(12) Pages: 2449-62

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Skeletal muscle adaptation 1 in response to mechanical stress in p130Cas-/- mice2013

    • Author(s)
      Akimoto T, Okuhira K, Aizawa K, Wada S, Honda H, Fukubayashi T, Uchida T
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 304

    • Related Report
      2013 Final Research Report
  • [Journal Article] Induction of pluripotent stem cells from primordial germ cells by single reprogramming factors2013

    • Author(s)
      Nagamatsu G. Kosaka T, Saito S, Honda H, Takubo K, Kinoshita T, Akiyama H, Sudo T, Horimoto K, Oya M, Suda T
    • Journal Title

      Stem Cells

      Volume: 31 Pages: 479-487

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7.2013

    • Author(s)
      Nagamachi A
    • Journal Title

      Cancer Cell

      Volume: 24 Issue: 3 Pages: 305-317

    • DOI

      10.1016/j.ccr.2013.08.011

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EED mutants impair polycomb repressive complex 2 in myelodysplastic syndrome and related neoplasms2012

    • Author(s)
      Ueda T, Sanada M, Matsui H, Yamasaki N, Honda Zi, Shih LY, Mori H, Inaba T, Ogawa S, Honda H
    • Journal Title

      Leukemia

      Volume: 26 Pages: 2557-2560

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors2012

    • Author(s)
      Zhang X, Kinuko Hirose K, Akahane K, Kuroda I, Honna H, Kagami K, Goi K, Nakamura K, Kobayashi M, Yagita H, Kurosawa H, Look AT, Honda H, Inaba T, Nakazawa S, Sugita K, Endo M, Inukai T
    • Journal Title

      Leukemia

      Volume: 26 Pages: 2483-2493

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation2012

    • Author(s)
      Ozaki Y, Matsui H, Asou H, Nagamachi A, Aki D, Honda H, Yasunaga S, Takihara Y, Yamamoto T, Izumi S, Ohsugi M, Inaba T
    • Journal Title

      Mol Cell

      Volume: 47 Pages: 694-706

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis2012

    • Author(s)
      Li Q, Guo H, Matsui H, Honda H, Inaba T, Sundberg JP, Sprecher E, Uitto J
    • Journal Title

      Exp Dermatol

      Volume: 21 Pages: 554-556

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor2012

    • Author(s)
      Sugihara E, Shimizu T, Kojima K, Ohishi N, Kai K, Ishizawa J, Nagata K, Hashimoto N, Honda H, Kanno M, Miwa M, Okada S, Andreeff M, Saya H
    • Journal Title

      Oncogene

      Volume: 31 Pages: 2849-2861

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ink4a and Arf are crucial factors in the determination of the cell of origin and the therapeutic sensitivity of Myc-induced mouse lymphoid tumor2012

    • Author(s)
      Sugihara E, Shimizu T, Kojima K, Ohishi N, Kai K, Ishizawa J, Nagata K, Hashimoto Nz, Kanno M, Miwa M, Okada S, Andreeff M, Saya H
    • Journal Title

      Oncogene

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cas-L regulates myeloid cell motility and suppresses progression of leukemia induced by p210Bcr/Abl2011

    • Author(s)
      Seo S, Nakamoto T, Takeshita M, Lu J, Sato T, Suzuki T, Kamikubo Y, Ichikawa M, Noda M, Ogawa S, Honda H, Oda H, Kurokawa M
    • Journal Title

      Cancer Sci

      Volume: 102 Pages: 2109-2117

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Samd9L gene : transcriptional regulation and tissue-specific expression in mouse development2011

    • Author(s)
      Jiang Q, Quaynor B, Sun A, Li Q, Matsui H, Honda H, Inaba T, Sprecher E, Uitto J
    • Journal Title

      J Invest Dermatol

      Volume: 131 Pages: 1428-1434

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation2011

    • Author(s)
      Honda H, Takubo K, Oda H, Kosaki K, Tazaki T, Yamasaki N, Miyazaki K, Moore KA, Honda Zi, Suda T, Lemischka IR
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108 Pages: 2468-2473

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Role of disease-related EED Ile363Met mutant in embryonic development and tumorigenesis2014

    • Author(s)
      Takeshi Ueda, Masashi Sanada, Hirotaka Matsui, Norimasa Yamasaki, Zen-ichiro Honda, Lee-Yung Shih, Hiraku Mori, Toshiya Inaba, Seishi Ogawa, and Hiroaki Honda
    • Organizer
      日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒストン脱メチル化酵素Fbxl10の脱制御による白血病発症機構の解析2013

    • Author(s)
      本田浩章
    • Organizer
      新学術領域がん支援冬期シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] MDSで同定されたポリコローム複合体構成因子EEDの機能欠失型変異体の解析2012

    • Author(s)
      上田健, 真田晶, 松井啓隆, 山崎憲政, 本田善一郎, 森啓, LEE-YUNG SHIH 稲葉俊哉, 小川誠司, 本田浩章
    • Organizer
      第74回日本血液学会
    • Place of Presentation
      京都
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of leukemogenic mechanisms induced by deregulation of a histone demethylase, Fbx1102011

    • Author(s)
      本田浩章
    • Organizer
      日本分子生物学会
    • Place of Presentation
      横浜(招待講演)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 骨髄異形成症候群におけるポリコローム複合体PRC構成因子EDDの機構欠失型変異2011

    • Author(s)
      上田健, 真田晶, 松井啓隆, 山崎憲政, 本田善一郎, 森啓, LEE-YUNG SHIH, 稲葉俊哉, 小川誠司, 本田浩章
    • Organizer
      第73回日本血液学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report
  • [Presentation] Different mechanisms through which Samd9L, a-7/7q-responsible gene, contributes to leukemogenesis2011

    • Author(s)
      長町安希子、松井啓隆、尾崎佑子、山崎憲政、小田秀明、稲葉俊哉、本田浩章
    • Organizer
      日本血液学
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] -7/7q-責任遺伝子候補 Samd9L2011

    • Author(s)
      長町安希子, 松井啓隆, 尾崎裕子, 山崎憲政, 小田秀明 , 稲葉俊哉 , 本田浩章
    • Organizer
      第73回日本血液学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Eed mutations impairing polycomb repressive complex 2 function in myelodysplastic syndrome2011

    • Author(s)
      上田健、真田昌、松井啓隆、山崎憲政、本田善一郎、Lee-Yung Shih、森啓、稲葉俊哉、小川誠司、本田浩章
    • Organizer
      日本血液学
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://home.hiroshima-u.ac.jp/sosai/top.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 広島大学原爆放射線医科学研究所・疾患モデル解析研究分野

    • URL

      http://home.hiroshima-u.ac.jp/sosai/top.html

    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://home.hiroshima-u.ac.jp/sosai/top.html

    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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