Characterization of tumorigenic stem cells in myeloid neoplasms

• Project/Area Number: 22249039
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: AKASHI Koichi 九州大学, 医学研究院, 教授 (80380385)
• Co-Investigator(Kenkyū-buntansha): MIYAMOTO Toshihiro 九州大学, 大学病院, 講師 (70343324) ; TAKENAKA Katsuto 九州大学, 大学病院, 講師 (30301295) ; IWASAKI Hiromi 九州大学, 大学病院, 准教授 (20403925)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥48,360,000 (Direct Cost: ¥37,200,000、Indirect Cost: ¥11,160,000); Fiscal Year 2012: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2010: ¥21,840,000 (Direct Cost: ¥16,800,000、Indirect Cost: ¥5,040,000)
• Keywords: 腫瘍性幹細胞 / 骨髄増殖性腫瘍 / 骨髄異形成症候群 / 異種移植 / マクロファージ寛容 / SIRPA / CD47 / 造血幹細胞

Research Abstract

To understand the property of tumorigenic stem cells in diverse myeloid neoplasms, it is necessary to develop an efficient xenotransplant model. We established a novel immunodeficient mouse strain that possessed a high capability to reconstitute human hem

Research Products

• [Journal Article] TIM-3 as a therapeutic target for malignant stem cells in acute myelogenous leukemia (2013)
  • Author(s): Kikushige Y, Akashi K
  • Journal Title: Ann NY Acad Sci Volume: 1266 Issue: 1 Pages: 118-123
  • DOI: 10.1111/j.1749-6632.2012.06550.x
  • 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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Engulfment of hematopoietic stem cel ls caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis (2012)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Selfrenewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia (2011)
  • Author(s): Kikushige Y, Ishikawa F, Miyamoto T, Shima T, Urata S, Yoshimoto G, Mort Y, lino T, Yamauchi T, Eta T, Niiro H, Iwasaki H, Takenaka K, and Akashi K
  • Journal Title: Cancer Cell Volume: 20(2) Issue: 2 Pages: 246-259
  • DOI: 10.1016/j.ccr.2011.06.029
  • Peer Reviewed
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. (2011)
  • Author(s): Oku S, Takenaka K, Kuriyama T, Shide K, Kumano T, Kikushige Y, Urata S, Yamauchi T, Iwamoto C, Shimoda HK, Miyamoto T, Nagafuji K, Kishimoto J, Shimoda K, Akashi K.
  • Journal Title: Br J Haematol Volume: 150(3) Issue: 3 Pages: 334-344
  • DOI: 10.1111/j.1365-2141.2010.08249.x
  • Peer Reviewed
• [Journal Article] Self-renewing hematopoietic stem cell is the primary target in pathogenesis ofhuman chronic lymphocytic leukemia. Cancer Cell (2011)
  • Author(s): Kikushige Y, et al
  • Journal Title: Cancer Cell Volume: 20-2 Pages: 246-259
  • Peer Reviewed
• [Journal Article] The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells (2011)
  • Author(s): Takashima S, et al
  • Journal Title: J Exp Med Volume: 208-2 Pages: 285-294
  • Peer Reviewed
• [Journal Article] Regenerating islet-derived 3-alpha is a biomarker ofgastrointestinal graft-versus-host disease (2011)
  • Author(s): Ferrara L, et al
  • Journal Title: Blood Volume: 118-25 Pages: 6702-6708
  • Peer Reviewed
• [Journal Article] The classification of mRNA expression levels by the phosphorylation state of RNAPII CTD based on a combined genome-wide approach (2011)
  • Author(s): Odawara J, et al
  • Journal Title: BMC Genomics Volume: 12 Pages: 516-516
  • Peer Reviewed
• [Journal Article] Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation (2011)
  • Author(s): Mori Y, et al
  • Journal Title: Biol Blood Marrow Transplant Volume: 18-3 Pages: 458-465
  • 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 childhood (2011)
  • Author(s): Ohga S., et al
  • Journal Title: J Clin Virol Volume: 51-1 Pages: 31-37
  • Peer Reviewed
• [Journal Article] Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission : Fukuoka BMT Group observations and a literature review (2011)
  • Author(s): Kamimura T, et al
  • Journal Title: Bone Marrow Transplant Volume: 46-6 Pages: 820-826
  • Peer Reviewed
• [Journal Article] The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells (2011)
  • Author(s): Takashima S, Kadowaki M, Aoyama K, Koyama M, Oshima T, Tomizuka K, Akashi K, Teshima T
  • Journal Title: J Exp Med Volume: 208(2) Pages: 285-94
  • Peer Reviewed
• [Journal Article] TIM-3 is a promising target to selec tively kill acute myeloid leukemia s tem cells (2010)
  • Author(s): Kikushige Y, Shima T 他7名
  • Journal Title: Cell Stem Cell Volume: 7巻 Issue: 6 Pages: 708-717
  • DOI: 10.1016/j.stem.2010.11.014
  • Peer Reviewed
• [Journal Article] TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells (2010)
  • Author(s): Kikushige Y, Shima T, Takayanagi SI, Urata S, Miyamoto T, Iwasaki H, Takenaka K, Teshima T, Tanaka T, Inagaki Y, Akashi K
  • Journal Title: Cell Stem Cell Volume: 7(6) Pages: 708-717
  • Peer Reviewed
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation (2010)
  • Author(s): Oku S, Takenaka K, Kuriyama T, Shide K, Kumano T, Kikushige Y, Urata S, Yamauchi T, Iwamoto C, Shimoda HK, Miyamoto T, Nagafuji K, Kishimoto J, Shimoda K, Akashi K
  • Journal Title: Br J Haematol Volume: 150(3) Pages: 334-344
  • Peer Reviewed
• [Journal Article] Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice (2010)
  • Author(s): Asakura S, Hashimoto D, Takashima S, Sugiyama H, Maeda Y, Akashi K, Tanimoto M, Teshima T
  • Journal Title: J Clin Invest Volume: 120(7) Pages: 2370-2378
  • NAID: 130004505744
  • Peer Reviewed
• [Journal Article] Enhanced expression of PCAF endows apoptosis resistance in cisplatin-resistant cells (2010)
  • Author(s): Hirano G, Izumi H, Kidani A, Yasuniwa Y, Han B, Kusaba H, Akashi K, Kuwano M, Kohno K
  • Journal Title: Mol Cancer Res Volume: 8(6) Pages: 864-872
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. (2010)
  • Author(s): Parmar K, Kim J, Sykes SM, Shimamura A, Stuckert P, Zhu K, Hamilton A, Deloach MK, Kutok JL, Akashi K, Gilliland DG, D'andrea A
  • Journal Title: Stem Cells Volume: 28(7) Pages: 1186-1195
  • 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 childhood
  • Author(s): Ohga S, Ishimura M, Yoshimoto G, Miyamoto T, Takada H, Tanaka T, Ohshima K, Ogawa Y, Imadome KI, Abe Y, Akashi K, Hara T
  • Journal Title: J Clin Virol Volume: (in press)
  • Peer Reviewed
• [Presentation] Transcription factor regulation of normal and malignant hematopoiesis. (2013)
  • Author(s): Akashi K
  • Organizer: 2013 USA-Japan Science Conference
  • Place of Presentation: Hawaii,USA
  • Year and Date: 2013-03-26
• [Presentation] 悪性造血器腫瘍における癌幹細胞の病理 (2012)
  • Author(s): 赤司浩一
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] 慢性リンパ性白血病幹細胞の特性と治療応用 (2012)
  • Author(s): 赤司浩一
  • Organizer: 第10回日本臨床腫瘍学会
  • Place of Presentation: 大阪
  • Year and Date: 2012-07-28
• [Presentation] 造血器悪性幹細胞の成立機序 (2012)
  • Author(s): 赤司浩一
  • Organizer: 第101回日本病理学会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] Transcription factor regulation in normal and malignant hematopoiesis (2011)
  • Author(s): Koichi Akashi
  • Organizer: 米国血液学会
  • Place of Presentation: San Diego、米国
  • Year and Date: 2011-12-10
• [Presentation] Origin of leukemic stem cells (2011)
  • Author(s): Koichi Akashi
  • Organizer: ドイツ造血幹細胞学会
  • Place of Presentation: Tubingen、ドイツ
  • Year and Date: 2011-09-07
• [Presentation] Leukemic stem cells (2011)
  • Author(s): Koichi Akashi
  • Organizer: ヨーロッパ血液学会
  • Place of Presentation: London、英国(招聘講演)
  • Year and Date: 2011-07-11
• [Presentation] Transcription factor regulation in normal and malignant hematopoiesis. (2011)
  • Author(s): Akashi K
  • Organizer: 第53回米国血液学会
  • Place of Presentation: SanDiego,USA
• [Presentation] Origin of leukemic stem cells (2011)
  • Author(s): Akashi K
  • Organizer: ドイツ造血幹細胞学会
  • Place of Presentation: Tubingen,Gemmany
• [Presentation] Leukemic stem cells (2011)
  • Author(s): Akashi K
  • Organizer: 第16回ヨーロッパ血液学会
  • Place of Presentation: London,UK
• [Presentation] 白血病幹細胞を考える (2010)
  • Author(s): 赤司浩一
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] 造血器悪性幹細胞の成立機構
  • Author(s): 赤司浩一
  • Organizer: 第101回日本病理学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Transcription Factor Regulation of Normal and Malignant Hematopoiesis
  • Author(s): Akashi K
  • Organizer: 2013USA-Japan Science Conference
  • Place of Presentation: Maui,Hawaii
  • Invited
• [Remarks] 九州大学第一内科
  • URL: http://www.lnai.med.kyushu-.ac.Jp
• [Remarks] 新学術領域研究「癌幹細胞を標的とする腫瘍根絶技術の新構築」
  • URL: http://www.cancer-tem-ell.com
• [Remarks] 新学術領域研究「癌幹細胞を標的とする腫瘍根絶技術の新構築」
  • URL: http://www.cancer-stem-cell.com/
• [Remarks] 九州大学医学部第一内科
  • URL: http://www.1nai.med.kyushu-u.ac.jp/
• [Remarks]
  • URL: http://www.1nai.med.kyushu-u.ac.jp/
• [Remarks]
  • URL: http://www.cancer-stem-cell.com/
• [Remarks]
  • URL: http://www.cancer-stem-cell.com/
• [Remarks]
  • URL: http://www.med.kyushu-u/ac.jp/intmedl/
• [Remarks]
  • URL: http://www.idenshi.co.jp/