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Study on pathophysiology and treatment of dendritic precursor cell derived myelodendritic cell leukemia

Research Project

Project/Area Number 11670986
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

TAKAHASHI Masuhiro  Faculty OF Medicine, Niigata University, Professor, 医学部, 教授 (90179531)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Tatsuo  Medical Hospital, Niigata University, Associate Professor, 医学部・附属病院, 助教授 (00272849)
NARITA Miwako  Faculty OF Medicine, Niigata University, Assistant, 医学部, 助手 (30281009)
小池 正  新潟大学, 医学部・附属病院, 助教授 (30170161)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsdendritic precursor cells / myelodendritic leukemia / leukemia derived dendritic cells / CTL line / anti-leukemic immunotherapy / myelodendric leukemia / dendritic cells / mupelodendritic leukemia / anti-leukemic immune-Therapy / 樹状細胞 / 急性白血病 / 白血病性樹状細胞 / CDla / CD83 / 混合白血球培養 / 抗原呈示能
Research Abstract

Objective : In order to elucidate the mechanism of immunological escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we tried to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia derived dendritic cells, we investigated leukemia cell-associated T cell anergy. Materials and Methods : Leukemia cells of 30 patients with AML were cultured with GM-CSF, IL-4, and TNF-α. Cultured leukemia cells were evaluated for antigen presenting ability by mixed leukocyte culture. Normal lymphocytes, which were co-cultured with leukemia blasts in 1st MLC, were cultured with leukemia derived dendritic cells in 2nd MLC. Results : In culture of leukemia cells from 21 out of 30 patients examined, cells with stellate morphology were observed and cell fraction with Cdla^+ and/or CD83^+ were demonstrated to be present in the culture. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated the antigen presenting ability in leukemia derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3 or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. Leukemic origin of dendritic cells were suggested by in situ hybridization. By being co-cultured with CD80-negative leukemia blasts, the response of normal lymphocytes to leukemia derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from the different individual as leukemia blasts. Conclusion : Escape of leukemia cells from anti-leukemia immunity was suggested to be associated with T cell anergy caused by leukemia blasts. In addition, the present study implied that leukemia derived dendritic cells could be applied efficiently in anti-leukemia immunotherapy.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(34 results)

All Other

All Publications (34 results)

  • [Publications] Narita M, Takahashi M, Liu A, Nikkuni K, Furukawa T, et al.: "Leukemia Blasts-Induced T cell Anergy Demonstrated by Leukemia Derived Dendritic Cells in Acute Myelogenous Leukemia"Exp Hematol. 29. 709-719 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Liu A, Zheng Z, Osman Y, et al.: "Generation of Dendritic Cells from Leukaomia Cells of a Patient with acute promyelocytic leukaemia by Culture with GM-CSF, IL-4 and TNF-a"Acta Haematologica. 106. 86-94 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Furukawa T, Sato N, Liu A, Abe T, et al.: "Mobilization of dendritic cell precursors in the peripheral blood of normal person primed with granulocyte-colony stimulating factor"Dendritic Cells. 11. 35-38 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toba K, Hanawa H, Watanabe K, Fuse I Takahashi M, et al.: "Erythroid involvement in CD36 deficiency"Exp Hematol. 29. 1194-1200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liu A, Takahashi M, Narita M. Fuse I, Zheng z, et al.: "Generation of functional and maturo dendritic cells from cord blood and bone marrow CD34^+ cells by two-step culture combined with caloium ionophore treatmeut"J Immunol Methods. 261. 49-63 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osman Y, Takahashi M, Zheng Z, Koike T, Toba K, Liu A, Furukawa T, Aoki S, Aizawa Y: "Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide : Its applicability for donor leukocyte transfusions in marrow grafted CML patients"Leukemia. 13. 166-174 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osman Y, Takahashi M, Zheng Z, Toba K, Liu A, Furukawa T, Aoki S, Aizawa Y, Koike T: "Activation of autologous or HLA-identical sibling cytotoxic T lymphocytes by blood derived dendritic cells pulsed with tumor cell extracts"Int J Oncol Oncol Rep. 6. 1057-1063 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi M, Osman Y, Zheng Z, Toba K, Liu A, Furukawa T, Narita M, Koike T, Aizawa Y: "Induction of bcr-abl peptide specific CTLs by priming lymphocytes with bcr-abl peptid pulsed dendritic cells"Dendritic Cells. 9. 29-32 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osman Y, Takahashi M, Zheng Z, Toba K, Liu A, Furukawa T, Narita M, Aizawa Y, Koike T, Shibata A: "Dendritic cells stimulate the expansion of PML-RAR α specific cytotoxic T-lymphocytes : Its applicability for antileukemia immunotherapy"J Exp Clin Cancer Res. 18. 485-492 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liu A, Takahashi M, Toba K, Zheng Z, Takahashi H, Suzuki N, Hashimoto S, Nikkuni K, Furukawa T, Aoki S, Koike T, Aizawa Y: "Regulation of the expression of MHC class I and class II by class II transactivator (CIITA) in hematopoietic cells"Hemat Oncol. 17. 149-160 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zheng Z, Takahashi M, Toba K, Liu A, Furukawa T, Koike T, Aizawa Y: "Generation of Dendritic Cells from Adherent cells of Cord Blood by culture with GM-CSF, IL-4 and TNF-α"J Hematotherapy & Stem Cell Research. 9. 445-456 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi M, Osman Y, Narita M, Zheng Z, Liu A, Nikkuni K, Furukawa T, Toba K, Koike T, Aizawa Y: "Induction of anti-leukemia or anti-myeloma cytotoxic T lymphocytes by priming with leukemia or myeloma cell extracts-pulsed dendritic cells"Dendritic Cells. 10. 27-30 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Liu A, Nikkuni K, Furukawa T, Toba K, Koyama S, Takai K, Sanada M, Aizawa Y: "Leukemia Blasts-Induced T cell Anergy Demonstrated by Leukemia Derived Dendritic Cells in Acute Myelogenous Leukemia"Exp Hematol. 29. 709-719 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Liu A, Zheng Z, Osman Y, Satoh N, Nikkuni K, Furukawa T, Toba K, Koike T, Aizawa Y: "Generation of Dendritic Cells from Leukaemia Cells of a Patient with acute promyelocytic leukemia by Culture with GM-CSF, IL-4 and TNF-a"Acta Haematologica. 106. 86-94 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Furukawa T, Sato N, Liu A, Abe T, Ayres FM, Toba K, Aizawa Y: "Mobilization of dendritic cell precursors in the peripheral blood of normal person primed with granulocyte-colony stimulating factor"Dendritic Cells. 11. 35-38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liu A, Takahashi M, Narita M, Fuse I, Zheng Z, Nikkuni K, Furukawa T, Toba K, Aizawa Y: "Generation of functional and mature dendritic cells from cord blood and bone marrow CD34^+ cells by two-step culture combined with calcium ionophore treatment"J Immunol Methods. 261. 49-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Fuse I, Aizawa Y: "Ca^<2+> ionophore-induced dendritic cell differentiation in a patient with defective Ca^<2+> ionophore-induced platelet aggregation"Br J Haematol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narita M, Takahashi M, Liu A, Nikkuni K, Furukawa T, et al.: "Leukemia Blasts-Induced T cell Anergy Demonstrated by Leukemia Derived Dendritic Cells in Acute Myelogenous Leukemia"Exp Hematol. 29. 709-719 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Narita M, Takahashi M, Liu A, Zheng Z, Osaman Y, et al.: "Generation of Dendritic Cells from Leukaemia Cells of a Patient with acute promyelocytic leukaeimia by Culture with GM-CSF, IL-4 and TNF-a"Acta Haematologica. 106. 86-94 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Narita M, Takahashi M, Furukawa T, Sato N, Liu A, Abe T, et al.: "Mobilization of dendritic cell precursors in the peripheral blood of normal person primed with granulocyte-colony stimulating factor"Dendritic Cells. 11. 35-38 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hashimoto, S Toba K, Aoki S, Tsuchiyama J, Takahashi M, et al.: "Acute T-lymphoblastic leukemia relapsed with the character of myeloid/NK cell precursor phenotype"Leuk Res. 26. 141-145 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toba K, Hanawa H, Watanabe K, Fuse I, Takahashi M, et al.: "Erythroid involvement in CD36 deficiency"Exp Hematol. 29. 1194-1200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zheng Z: "Generation of dendritic cells from adherent cells of cord blood by culture with GM-CSF IL-4 and TNF-a."J Hematoth Stem Cell. 9. 445-446 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi M: "Induction of anti-leukemia or anti-myeloma cytotoxic T lymphocytes by priming with leukemia..."Dendritic Cells. 10. 27-30 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Narita M: "Blasts-induced T cell anergy demonstrated by leukemia derived dendritic cells in AML."Exp Hematol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Toba K: "Cell Kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY."Eur J Haematol. 64. 225-230 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋益廣: "白血病細胞の抗腫瘍免疫からの回避と白血病由来樹状細胞によるその克服"医学のあゆみ. 194(14). 1253-1260 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋益廣: "IL-10.LIV-B処理樹状細胞によるT細胞アネルギー誘導"臨床免疫. 34(5). 567-577 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasser OSMAN, Masuhiro TAKAHASHI, Zhiyin ZHENG, Tadashi KOIKE, Ken TOBA, Aichun LIU, Tatuo FURUKAWA: "Generation of bcr-ab1 specific cytotoxic T-Iymphocytes by using dendritic cells pulsed with bcr-ab1 (b3a2) peptide: Its applicability for donor leukocyte transfusions in marrow grafted CML patients"Leukemia. 13. 166-174 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasser Osman, Masuhiro Takahashi, Zhiyin Zheng, Ken Toba, Aichun Liu, Tatsuo Furukawa, Sadao Aoki, Yoshifusa Aizawa: "Activation of autologous or HLA-identical sibling cytotoxic T Iymphocytes by blood derived dendritic cells pulsed with tumor cell extracts"Int J Oncol Rep. 6. 1057-1063 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masuhiro Takahashi, Yasser Osman, Zhiyin Zheng, Aichun Liu, Tatsuo Furukawa, Ken Toba, Tadashi Koike: "Induction of bcr-ab1 peptide specific CTLs by priming lymphocytes with bcr-ab1 peptid pulsed dendritic cells"Dendritic Cells. 9. 29-32 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yasser OSMAN, Masuhiro TAKASHI, Zhiyin ZHENG, Ken TOBA, Aichun LIU, Tatuo FURUKAWA, Sadao AOKl: "Dendritic cells stimulate the expansion of PML-RAR α specific cytotoxic T-lymphocytes: Its applicability for antileukemia immunotherapy"J Exp Clin Cancer Res. 17. 485-492 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Aichun Liu, Masuhiro Takahashi, Ken Toba, Zhiyin Zheng, Hidenobu Takahashi, Noriatsu Suzuki, Shigeo Hashimoto: "Regulation of the expression of MHC class I and class II by class II transactivator (CIITA) in hematopoietic cells"Hemat Oncol. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] ZHIYlN ZHENG, MASUHIRO TAKAHASHI, KEN TOBA, AICHUN LIU, TATSUO FURUKAWA, TADASHI KOIKE: "Generation of Dendritic Cells from Adherent cells of Cord Blood by culture with GM-CSF, IL-4 and TNF- α"J Immunotherapy. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-03-31   Modified: 2016-04-21  

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