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Gene mutations in hematopoietic stem cells of chronic lymphocytic leukemia

Research Project

Project/Area Number 24659462
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKyushu University

Principal Investigator

MIYAMOTO TOSHIHIRO  九州大学, 大学病院, 講師 (70343324)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords慢性リンパ性白血病 / 造血幹細胞 / 白血化機構 / 幹細胞 / 白血病モデルマウス / エキソンシーケンス / 白血化
Outline of Final Research Achievements

Chronic lymphocytic leukemia (CLL) is a mature B cell malignancy, which has been considered to originate from mature B cells. We reported that even in CLL, very primitive hematopoietic stem cells (HSCs) should be involved in the pathogenesis of CLL. In this study, we tried to identify the somatic mutations acquired in primary CLL cells, and test whether such somatic mutations could be detected within HSCs of the CLL patients. We found that some of the identical somatic mutations acquired in CLL cells could be traced back to CD34+ human hematopoietic stem progenitor cells (HSPCs) and myeloid cells of the CLL patients. These results collectively suggest that early mutations associated with CLL pathogenesis should be acquired and accumulated within the self-renewing HSCs in human, and these abnormal pre-leukemic HSCs play a significant role in the multi-step leukemia progression processes of CLL.

Report

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

    (22 results)

All 2015 2014 2013 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (4 results) (of which Invited: 3 results) Book (4 results) Remarks (2 results)

  • [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.2015

    • Author(s)
      Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T
    • Journal Title

      Blood

      Volume: 未定

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.2015

    • Author(s)
      Kikushige Y, Miyamoto T
    • Journal Title

      Int J Hematol

      Volume: 未定

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor.2015

    • Author(s)
      Miyawaki K, Arinobu Y, Iwasaki H, Kohno K, Tsuzuki H, Iino T, Shima T, Kikushige Y, Takenaka K, Miyamoto T, Akashi K.
    • Journal Title

      Stem Cells

      Volume: 33 Issue: 3 Pages: 976-87

    • DOI

      10.1002/stem.1906

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics of patients with development of large granular lymphocyte expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation.2015

    • Author(s)
      Ito Y, Miyamoto T, Kamimura T, Aoki K, Henzan H, Aoki T, Shiratsuchi M, Kato K, Nagafuji K, Ogawa R, Eto T, Iwasaki H, Akashi K.
    • Journal Title

      Clin Lymphoma Myeloma Leuk.

      Volume: 15 Issue: 3 Pages: 47-54

    • DOI

      10.1016/j.clml.2014.09.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.2014

    • Author(s)
      Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
    • Journal Title

      Exp. Hematol.

      Volume: 42 Issue: 11 Pages: 955-65

    • DOI

      10.1016/j.exphem.2014.07.267

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis.2014

    • Author(s)
      Kikushige Y, Miyamoto T
    • Journal Title

      Int J Hematol

      Volume: 100 Issue: 4 Pages: 335-340

    • DOI

      10.1007/s12185-014-1651-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients.2014

    • Author(s)
      Takashima S, Miyamoto T, Kadowaki M, Ito Y, Aoki T, Takase K, Shima T, Yoshimoto G, Kato K, Muta T, Shiratsuchi M, Takenaka K, Iwasaki H, Teshima T, Kamimura T, Akashi K.
    • Journal Title

      Int J Hematol

      Volume: 100 Issue: 2 Pages: 159-164

    • DOI

      10.1007/s12185-014-1611-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Quantification of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic stem cell transplantation.2013

    • Author(s)
      Shima T
    • Journal Title

      Blood

      Volume: 121 Issue: 5 Pages: 840-848

    • DOI

      10.1182/blood-2012-02-409607

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment.2013

    • Author(s)
      Yamauchi T
    • Journal Title

      Blood

      Volume: 121 Issue: 8 Pages: 1316-1325

    • DOI

      10.1182/blood-2012-06-440354

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.2013

    • Author(s)
      Takamatsu H, Ogawa Y, Kobayashi N, Obata K, Narisawa T, Nakayama K, Munemoto S, Aoki G, Ohata K, Kumano Y, Ozaki J, Murata R, Kondo Y, Terasaki Y, Kurokawa T, Miyamoto T, Shimizu N, Fukushima T, Yoshida A, Ueda T, Yoshida T, Nakao S
    • Journal Title

      Exp Hematol

      Volume: 41 Issue: 10 Pages: 894-902

    • DOI

      10.1016/j.exphem.2013.05.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluating the association between histological manifestations of cord colitis syndrome with GVHD.2013

    • Author(s)
      Shimoji S, Kato K, Eriguchi Y, Takenaka K, Iwasaki H, Miyamoto T, Oda Y, Akashi K, Teshima T
    • Journal Title

      Bone Marrow Transplant

      Volume: 48 Issue: 9 Pages: 1249-1252

    • DOI

      10.1038/bmt.2013.44

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.2013

    • Author(s)
      Miyamoto T, Yoshimoto G, Kamimura T, Muta T, Takashima S, Ito Y, Shiratsuchi M, Choi I, Kato K, Takenaka K, Iwasaki H, Takamatsu Y, Teshima T, Akashi K.
    • Journal Title

      Int J Hematol

      Volume: 98 Issue: 3 Pages: 337-345

    • DOI

      10.1007/s12185-013-1402-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 造血器腫瘍における治療選択と臨床検査2014

    • Author(s)
      宮本敏浩
    • Organizer
      日本臨床検査医学会学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-11-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨髄増殖性腫瘍の治療2014

    • Author(s)
      宮本敏浩
    • Organizer
      日本血液学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-11-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] AML stem cells2013

    • Author(s)
      宮本敏浩
    • Organizer
      第75回日本血液学会総会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 造血幹細胞移植前治療のUpdate2013

    • Author(s)
      宮本敏浩
    • Organizer
      第75回日本血液学会総会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2013 Research-status Report
  • [Book] 白血病診療Q&A 一つ上を行く診療の実践2015

    • Author(s)
      宮本敏浩
    • Total Pages
      10
    • Publisher
      中外医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 血液疾患最新の治療 2014-20162014

    • Author(s)
      吉本五一、宮本敏浩
    • Total Pages
      7
    • Publisher
      南江堂
    • Related Report
      2014 Annual Research Report
  • [Book] Patient Surveillance After Cancer Treatment2013

    • Author(s)
      Miyamoto T
    • Total Pages
      538
    • Publisher
      Humana Press
    • Related Report
      2013 Research-status Report
  • [Book] Annual Review 血液 20132013

    • Author(s)
      菊繁吉謙、宮本敏浩,赤司浩一
    • Total Pages
      9
    • Publisher
      中外医学社
    • Related Report
      2012 Research-status Report
  • [Remarks] 九州大学第一内科ホームページ

    • URL

      http://www.1nai.med.kyushu-u.ac.jp

    • Related Report
      2014 Annual Research Report
  • [Remarks] 九州大学医学部第一内科ホームページ

    • URL

      http://www.1nai.med.kyushu-u.ac.jp

    • Related Report
      2013 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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