• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The elucidation of the mechanisms of growth arrest and apoptosis in myeloma cells induced by PU.1 and its utility for myeloma treatment

Research Project

Project/Area Number 23591395
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionKumamoto University

Principal Investigator

OKUNO YUTAKA  熊本大学, 大学院生命科学研究部, 准教授 (80363539)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords多発性骨髄腫 / PU.1 / 細胞増殖停止 / 細胞死 / 癌抑制遺伝子 / B細胞リンパ腫 / M蛋白 / 腫瘍抑制因子 / ホジキンリンパ腫 / p21 / TRAIL
Research Abstract

We conditionally expressed PU.1 in classical Hodgkin lymphoma cell lines, L-428 and KM-H2, and identified that PU.1 induced growth arrest and apoptosis in these cells. Lentiviral transduced PU.1 expression also induced apoptosis in primary Hodgkin lymphoma cells from patients. Therefore, we concluded that PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.
We previously conditional expressed PU.1 also induces growth arrest and apoptosis in myeloma cell lines, U266 and KMS12PE. To test whether PU.1 is a tumor suppressor in mature B cells, including plasma cells, in vivo, we generated conditional PU.1 knockout mice in post germinal center B cells and plasma cells. At the age of 18-24 months, some of these mice shows a proliferation plasma cells in spleen and/or bone marrow. Therefore, PU.1 might be a tumor suppressor in plasma cells in vivo. We are still analyzing these mice.

Report

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

    (29 results)

All 2014 2013 2012 2011

All Journal Article (16 results) (of which Peer Reviewed: 13 results) Presentation (7 results) Book (6 results)

  • [Journal Article] PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells2013

    • Author(s)
      Yuki H, Ueno S, Tatetsu H, Niiro H, Iino T, Endo S, Kawano Y, Komohara Y, Takeya M, Hata H, Okada S, Watanabe T, Akashi K, Mitsuya H and Okuno Y
    • Journal Title

      Blood

      Volume: 121(6) Pages: 962-970

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia reduces CD138 expression and induces an immature and stem cell-like transcriptional program in myeloma cells2013

    • Author(s)
      Kawano Y, Kikukawa Y, Fujiwara S, Wada N, Okuno Y, Mitsuya H, Hata H
    • Journal Title

      Int J Oncol

      Volume: 43(6) Pages: 1809-16

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] PDK1 inhibition is a novel therapeutic target in multiple myeloma2013

    • Author(s)
      Fujiwara S, Kawano Y, Yuki H, Okuno Y, Nosaka K, Mitsuya H and Hata H
    • Journal Title

      Br J Cancer

      Volume: 108(1) Pages: 170-178

    • Related Report
      2013 Final Research Report
  • [Journal Article] PDK1 inhibition is a novel therapeutic target in multiple myeloma.2013

    • Author(s)
      Fujiwara, S., Kawano, Y., Yuki, H., Okuno, Y., Nosaka, K., Mitsuya, H., and Hata, H.
    • Journal Title

      Br J Cancer

      Volume: 108 Issue: 1 Pages: 170-178

    • DOI

      10.1038/bjc.2012.527

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PU.1 is a tumor suppressor for B cell malignancies2012

    • Author(s)
      Okuno Y and Yuki H
    • Journal Title

      Oncotarget

      Volume: 3(12) Pages: 1495-1496

    • Related Report
      2013 Final Research Report
  • [Journal Article] Three cases of aggressive natural killer cell leukemia with a lethal hemorrhagic complication2012

    • Author(s)
      Okuno Y, Tatetsu H, Nosaka K and Mitsuya H
    • Journal Title

      J Clin Exp Hematop

      Volume: 52(2) Pages: 101-106

    • NAID

      10031120433

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] TRAIL produced from multiple myeloma cells is associated with osteolytic markers2012

    • Author(s)
      Kawano Y, Ueno S, Abe M, Kikukawa Y, Yuki H, Iyama K, Okuno Y, Mitsuya H and Hata H
    • Journal Title

      Oncology Reports

      Volume: 27 Pages: 39-44

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide2012

    • Author(s)
      Kawano Y, Fujiwara S, Wada N, Izaki M, Yuki H, Okuno Y, Iyama K, Yamasaki H, Sakai A, Mitsuya H and Hata H
    • Journal Title

      Int J Oncol

      Volume: 41(3) Pages: 876-884

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.2012

    • Author(s)
      Yuki H
    • Journal Title

      Blood

      Volume: 121 Issue: 6 Pages: 962-970

    • DOI

      10.1182/blood-2012-05-431429

    • Related Report
      2013 Annual Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] PU.1 is a tumor suppressor for B cell malignancies.2012

    • Author(s)
      Okuno, Y., and Yuki, H.
    • Journal Title

      Oncotarget

      Volume: 3 Pages: 1495-1496

    • Related Report
      2012 Research-status Report
  • [Journal Article] Three cases of aggressive natural killer cell leukemia with a lethal hemorrhagic complication.2012

    • Author(s)
      Okuno, Y., Tatetsu, H., Nosaka, K., and Mitsuya, H.
    • Journal Title

      J Clin Exp Hematop

      Volume: 52 Pages: 101-106

    • NAID

      10031120433

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] TRAIL produced from multiple myeloma cell is associated with osteolytic markers.2012

    • Author(s)
      1. Kawano Y
    • Journal Title

      Oncol Rep

      Volume: 27 Pages: 39-44

    • DOI

      10.3892/or.2011.1491

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide.2012

    • Author(s)
      Kawano, Y., Fujiwara, S., Wada, N., Izaki, M., Yuki, H., Okuno, Y., Iyama, K., Yamasaki, H., Sakai, A., Mitsuya, H., et al.
    • Journal Title

      Int J Oncol

      Volume: 41 Issue: 3 Pages: 876-884

    • DOI

      10.3892/ijo.2012.1545

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three Cases of Aggressive Natural Killer Cell Leukemia with a Lethal Hemorrhagic Complication2012

    • Author(s)
      Yutaka Okuno, Hiro Tatetsu, Kisato Nosaka, and Hiroaki Mitsuya
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: In press

    • NAID

      10031120433

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element2011

    • Author(s)
      Levantini E, Lee S, Radomska H, Hetherington C, Alberich-Jorda M, Amabile G, Zhang P, Gonzalez D, Zhang J, Basseres D, Wilson N, Koschmieder S, Huang G, Zhang D, Ebralidze A, Bonifer C, Okuno Y, Gottgens B, Tenen DG
    • Journal Title

      EMBO J

      Volume: 30(19) Pages: 4059-4070

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element2011

    • Author(s)
      Levantini, E. Lee, S. Radomska, HS. Hetherington, CJ. et al.
    • Journal Title

      EMBO Journal

      Volume: 30 Pages: 4059-70

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Successful treatment by VRCD therapy of multiple myeloma (MM) patients refractory to RCD or VCD2013

    • Author(s)
      Yutaka Okuno, Eiko Miyagawa, Rie Furuta, Shinya Hirata, Hiroyuki Hata, Hiroaki Mitsuya
    • Organizer
      日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2013-10-11
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Conditional knockout of PU.1 in plasma cells results in monoclonal gammopathy2013

    • Author(s)
      Shinya Endo, Hiromichi Yuki, Yoshihiro Komohara, Shikiko Ueno, Hiro Tatetsu, Motohiro Takeya, Seiji Okada, Koichi Akashi, Daniel G Tenen, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2013-10-11
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] IRF4 down-regulation may be involved in PU.1-induced growth arrest/apoptosis in myeloma cells2013

    • Author(s)
      Niina Ueno , Shikiko Ueno, Hiro Tatetsu, Hiromichi Yuki , Hiroyuki Hata, Tadafumi Iino, Hiroaki Niiro, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      日本血液学会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2013-10-11
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells2012

    • Author(s)
      Hiromichi Yuki , Shikiko Ueno, Hiro Tatetsu, Hiroaki Niiro, Hiroyuki Hata, Seiji Okada, Toshiki Watanabe, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      日本血液学会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2012-10-19
    • Related Report
      2013 Final Research Report
  • [Presentation] PU.1 is a potent tumor suppressor for classical Hodgkin lymphoma cells2012

    • Author(s)
      Hiromichi Yuki , Shikiko Ueno, Hiro Tatetsu, Hiroaki Niiro, Hiroyuki Hata, Seiji Okada, Toshiki Watanabe, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      日本血液学会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2012 Research-status Report
  • [Presentation] PU.1-induced growth arrest and apoptosis in classical Hodgkin lymphoma cells2011

    • Author(s)
      Hiromichi Yuki , Shikiko Ueno, Hiroaki Niiro, Hiro Tatetsu, Hiroyuki Hata, Toshiki Watanabe, Seiji Okada, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      アメリカ血液学会
    • Place of Presentation
      サンディエゴ
    • Year and Date
      2011-12-05
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Presentation] PU.1-induced growth arrest and apoptosis in classical Hodgkin lymphoma cell lines2011

    • Author(s)
      Hiromichi Yuki, Shikiko Ueno, Hiro Tatetsu, Hiroaki Niiro, Hiroyuki Hata, Toshiki Watanabe, Koichi Akashi, Hiroaki Mitsuya, Yutaka Okuno
    • Organizer
      日本血液学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-15
    • Related Report
      2013 Final Research Report 2011 Research-status Report
  • [Book] 血液疾患最新の治療2014-2016, 多発性骨髄腫2014

    • Author(s)
      奥野豊、畑裕之
    • Total Pages
      373
    • Publisher
      南江堂
    • Related Report
      2013 Final Research Report
  • [Book] みのがしてはならない血液疾患病理からみた44症例2014

    • Author(s)
      菰原義弘、奥野豊、竹屋元裕
    • Total Pages
      278
    • Publisher
      医学書院
    • Related Report
      2013 Final Research Report
  • [Book] 血液疾患最新の治療2014-2016 "多発性骨髄腫”2014

    • Author(s)
      奥野 豊、畑 裕之
    • Total Pages
      373
    • Publisher
      南江堂
    • Related Report
      2013 Annual Research Report
  • [Book] みのがしてはならない血液疾患 病理からみた44症例2014

    • Author(s)
      菰原 義弘、奥野 豊、竹屋 元裕
    • Total Pages
      278
    • Publisher
      医学書院
    • Related Report
      2013 Annual Research Report
  • [Book] 血液症候群(第2版)III2013

    • Author(s)
      奥野豊
    • Total Pages
      767
    • Publisher
      日本臨床社
    • Related Report
      2013 Final Research Report
  • [Book] 血液症候群(第2版)III2013

    • Author(s)
      奥野 豊
    • Total Pages
      767
    • Publisher
      日本臨牀社
    • Related Report
      2013 Annual Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi