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Target TIM-3 to eradicate AML stem cells

Research Project

Project/Area Number 23390254
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) AKASHI Koichi  九州大学, 大学院医学研究院, 教授 (80380385)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords白血病 / 幹細胞 / TIM-3 / 標的治療 / TIM-3
Outline of Final Research Achievements

We have previously reported that T-cell immunoglobulin mucin-3 (TIM-3) is expressed on surface of self-renewing leukemic stem cells (LSCs) in acute myeloid leukemia (AML). In this study, we focused on TIM-3 ligands including galectin-9 and HMGB-1 to clarify the function of TIM-3 in human AML. Here, we show that TIM-3 and its ligand, galectin-9, constitutes an autocrine loop critical for human AML LSC development; galectin-9 is highly expressed in primary AML/LSCs, and these AML/LSCs secrete galectin-9 in an autocrine manner. Furthermore, we found that TIM-3/galectin-9 interaction induced the activation of NF-kB pathway in primary TIM-3+ AML cells. These results collectively suggest that TIM-3 and galectin-9 constitutes very unique autocrine stimulatory signaling machinery, which should contribute to the cell autonomous activation of NF-kB pathway in primary AML/LSCs.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (23 results) (of which Peer Reviewed: 23 results,  Acknowledgement Compliant: 3 results,  Open Access: 4 results) Presentation (8 results) (of which Invited: 4 results) Book (3 results) Remarks (2 results)

  • [Journal Article] A Single high-resolution HLA mismatch has a similar adverse impact on the outcome of related hematopoietic stem cell transplantation as a single low-resolution HLA mismatch.2015

    • Author(s)
      Fuji S, Kanda J, Kato S, Ikegame K, Morishima S, Miyamoto T, Hidaka M, Kubo K, Miyamura K, Tsudo M, Kobayashi H, Maesako Y, Eto T, Adachi S, Ichinohe T, Atsuta Y, Kanda Y.
    • Journal Title

      Am J Hematol

      Volume: 未定 Issue: 7 Pages: 618-623

    • DOI

      10.1002/ajh.24028

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [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] Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study.2015

    • Author(s)
      Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R
    • Journal Title

      Br J Haematol

      Volume: 未定 Issue: 5 Pages: 672-682

    • DOI

      10.1111/bjh.13338

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors prognostic of eligibility for allogeneic HCT among older patients with AML-CR1 and adverse- or intermediate-risk cytogenetics.2015

    • Author(s)
      Yamasaki S, Yoshimoto G, Ogawa R, Aoki K, Higuchi M, Harada N, Arima F, Kondo S, Matubara F, Takahashi T, Uike N, Miyamoto T, Okamura S, Akashi K; for the Fukuoka Blood and Marrow Transplantation Group
    • Journal Title

      Ann Hematol

      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] Impact of HLA allele mismatch on the clinical outcome in serologically matched related hematopoietic SCT.2014

    • Author(s)
      Fuji S, Kanda J, Kato S, Ikegame K, Morishima S, Miyamoto T, Hidaka M, Kubo K, Miyamura K, Ohashi K, Kobayashi H, Maesako Y, Adachi S, Ichinohe T, Atsuta Y, Kanda Y; HLA Working Group of Japan Society for Hematopoietic Cell Transplantation.
    • Journal Title

      Bone Marrow Transplant

      Volume: 49 Issue: 9 Pages: 1187-1192

    • DOI

      10.1038/bmt.2014.141

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [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] Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma.2014

    • Author(s)
      Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, Fujimoto K, Yamamoto K, Miyamoto T, Uike N, Tanimoto M, Tsukasaki K, Ishizawa K, Suzumiya J, Inagaki H, Tamura K, Akinaga S, Tomonaga M, Ueda R.
    • Journal Title

      J Clin Oncol

      Volume: 32 Issue: 11 Pages: 1157-1163

    • DOI

      10.1200/jco.2013.52.0924

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The BALB/c-specific polymorphic SIRPA enhances its affinity for human CD47, inhibiting phagocytosis against human cells to promote xenogeneic engraftment.2014

    • Author(s)
      Iwamoto C
    • Journal Title

      Exp Hematol

      Volume: 42 Issue: 3 Pages: 163-171

    • DOI

      10.1016/j.exphem.2013.11.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.2014

    • Author(s)
      Koyama M, Hashimoto D, Nagafuji K, Eto T, Ohno Y, Aoyama K, Iwasaki H, Miyamoto T, Hill GR, Akashi K, Teshima T.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 2014 Issue: 1 Pages: 110-115

    • DOI

      10.1038/bmt.2013.134

    • NAID

      120005460247

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 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 Annual Research Report 2012 Annual Research 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 Annual Research Report 2012 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High incidence and severity of injection site reactions in the first cycle compared with subsequent cycles of subcutaneous bortezomib.2013

    • Author(s)
      Kamimura T, Miyamoto T, Yokota N, Aoki T, Ito Y, Akashi K.
    • Journal Title

      Int J Hematol

      Volume: 98 Issue: 6 Pages: 694-701

    • DOI

      10.1007/s12185-013-1469-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical outcomes of allogeneic stem cell transplantation for relapsed or refractory follicular lymphoma: a retrospective analysis by the Fukuoka Blood and Marrow Transplantation Group.2013

    • Author(s)
      107 Ito Y, Miyamoto T, Kamimura T, Takase K, Henzan H, Sugio Y, Kato K, Ohno Y, Eto T, Teshima T, Akashi K
    • Journal Title

      Int J Hematol

      Volume: 98 Issue: 4 Pages: 463-471

    • DOI

      10.1007/s12185-013-1430-9

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Higher incidence of injection site reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen.2013

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

      Eur J Haematol

      Volume: 90 Issue: 2 Pages: 157-161

    • DOI

      10.1111/ejh.12055

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engulfment of hematopoietic stem cel ls caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis2012

    • Author(s)
      Kuriyama T, Takenaka K 他12名
    • Journal Title

      Blood

      Volume: 120巻 Issue: 19 Pages: 4058-4067

    • DOI

      10.1182/blood-2012-02-408864

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia2011

    • Author(s)
      Kikushige Y, Miyamoto T, Akashi K, et al
    • Journal Title

      Cancer Cell

      Volume: 20 Pages: 246-259

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission : Fukuoka BMT Group observations and a literature review2011

    • Author(s)
      Kamimura T, Miyamoto T, Akashi K, et al
    • Journal Title

      Bone Marrow Transplantation

      Volume: 46 Pages: 820-826

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clonal origin of Epstein-Barr virus (EBV-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood2011

    • Author(s)
      Ohga S, Miyamoto T, Akashi K, et al
    • Journal Title

      J Clin Virol

      Volume: 51 Pages: 31-37

    • Related Report
      2011 Annual Research 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
      2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 高齢者造血器腫瘍に対する最新の治療2014

    • Author(s)
      宮本敏浩
    • Organizer
      日本老年医学学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-06-14
    • 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 Annual Research 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 Annual Research Report
  • [Presentation] Mobilization of allogeneic and autologous peripheral blood stem cells2012

    • Author(s)
      Miyamoto T
    • Organizer
      Asian Workshop for Hematopoietic Stem Cell Transplantation 2012
    • Place of Presentation
      Kumamoto
    • Related Report
      2012 Annual Research Report
  • [Presentation] Nilotinib in CML patients with suboptimal response to imatinib: early results from the SENSOR study2012

    • Author(s)
      Miyamoto T
    • Organizer
      第74回 日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] TIM-3 Is a Promising Target to Eradicate Acute Myeloid Leukemia Stem Cells Sparing Normal Hematopoietic stem Cells2011

    • Author(s)
      Miyamoto T, Kikushige Y, Shima T, Akashi K
    • Organizer
      53^<rd> American Society of Hematology Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2011-12-12
    • Related Report
      2011 Annual Research Report
  • [Book] 血液疾患最新の治療2014

    • Author(s)
      吉本五一、宮本敏浩
    • Total Pages
      10
    • 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 Annual Research Report
  • [Book] Annual Review 血液 20122012

    • 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 Annual Research 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 Annual Research Report

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

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