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Autologous graft for chronic myelogenous leukemia : Induction of apoptosis and selective elimination of Ph cells by hyperthermic treatment.

Research Project

Project/Area Number 06557062
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section試験
Research Field Hematology
Research InstitutionNiigata University

Principal Investigator

KISHI Kenji (1995-1996)  First Department of Internal Medicine School of Medicine, Niigata University, Lecture, 医学部附属病院, 講師 (30186209)

森山 美昭 (1994)  新潟大学, 医学部付属病院, 助教授 (00018706)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Masuhiro  Department of Medical Technology, College of Biomedical Technology, Niigata Univ, 医療技術短期大学部, 教授 (90179531)
岸 賢治  新潟大学, 医学部付属病院, 助手 (30186209)
Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordschronic myelogenous leukemia / autologous graft / in vitro purging / hyperthermic treatment / marrow culture / interferon / AZT / quercetin / hypertheraic treatment / 慢性骨髄性白血病 / 温熱法 / 自家骨髄移植 / 腫瘍細胞の生体外除去 / アポトーシス / 造血幹細胞 / 骨髄長期培養 / 腫瘍細胞の主体外除去 / 熱ショック蛋白
Research Abstract

As an alternative treatment with allogeneic bone marrow transplantation, the possibility of autologous stem cell transplantation for chronic myelogenous leukemia (CML) was studied. The most critical problem in this study is how to purify normal stem cells from autologous marrow or blood cells. Although normal stern cells are present in these patients in chronic phase, absolute amount of these cells are very small and undetectable by regular chromosome analysis.
In the first two reports, we investigated the effect of long-term marrow culture (LTMC) to eliminate leukemic clones. In the first report, we followed the previous report that appearance of Philadelphia chromosome (Ph) negative clones was observed after LTMC of CML patients. We found that addition of interferon-alpha (IFNalpha) in LTMC preferentially decrease Ph cells. In the second study, we investigated the frequencies of leukemic clones in suspending- and adherent- fraction of LTMC by reverse transcriptional-polymerase chain r … More eaction (RT-PCR) for bcr-abl, CML specific transcript, and chromosome analysis of a single progenitor derived colony. Addition of IFNalpha in LTMC of CML bone marrow accelerated the elimination of leukemic clones preferentially in the adherent fraction of the culture.
In the third presentation, we investigated the effect of hyperthermic treatment on clonogenic growth of Ph^+ leukemia cell lines, K562 and KU812. Hyperthermic treatment suppressed the clonogenic activities of both cell lines. Addition of AZT,IFNalpha, TNF,and quercetin enhanced the effect of hyperthermic clonogenic inhibition. The optimal in vitro hyperthermia purging technique is heating at 42゚C for 1 hour with combined IFN-alpha (100 U/ml) and AZT (0.5 muM) or quercetin (50 muM/ml), depending on the sensitivity of the CML cells to be eliminated. Effect of hyperthermia purging was associated with cellular apoptosis shown by DNA ladder formation in agarose electrophoresis.
For further clinical application of these technique, ex vivo expansion of human hematopoietic stem cells is necessary because only a small number of normal stem cells are available after culture. The last section in the second paper is showing the results of preliminary experiment in this field. Our data represented a possibility of expansion of human hematopoietic progenitors in vitro. Less

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Sato N, Kishi K, et al: "Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease." Bone Marrow Transplantation. 16. 303-305 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 瀧澤 淳、岸 賢治、他: "Fanconi貧血と思われる再生不良性貧血に続発した急性骨髄性白血病に親子間同種骨髄移植を施行した1症例." 臨床血液. 36. 615-620 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岸 賢治: "移植後の合併症とその対策、再発とその対策." 血液・腫瘍科. 31. 284-290 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 岸 賢治、他: "寛解導入療法と骨髄移植における日和見感染症予防の具体的方法とその根拠(新潟大学第一内科一般病棟および無菌室における予防法)" 血液・腫瘍科. 33. 226-231 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] "Second Allogeneic Bone Marrow Transplantation for Post-transplant Leukemia Relapse ; Results of a Survey of Sixty-Six Cases in 24 Japanese Institutes." Bone Marrow Transplantation. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 鈴木訓充、岸 賢治、他: "慢性骨髄性白血病における骨髄長期培養では正常前駆細胞は付着細胞層に多く存在する-インターフェロンの効果-" 新潟医学会雑誌. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato N,Kishi K,Yagisawa K,Kasama J,Karasawa R,Shimada H,Nishi S,Ueno M,Ito K,Koike T,Takahashi H,Moriyama Y,Arakawa M,Shibata A: Bone Marrow Transplantation. 16. 303-305 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takizawa J,Kishi K,Moriyama Y,Hashimoto S,Gotoh T,Higuchi W,Wada K,Narita M,Aoki S,Takahashi M,Koike T,Shibata A.: "Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father" Japanese Journal of Clinical Hematology. 36. 615-20 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kishi K: "Prophylaxis and treatment for leukemia relapse after bone marrow transplantation." Hematology & Oncology. 31(sup). 284-290 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kishi K,Ishimura C,Motoyama H,Shimokoshi I,Koike T: "Procedures and their effects of prophylaxis for oppotunistic infections during remission induction and bone marrow transplantation" Hematology & Oncology. 33. 226-231 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki N,Koike T,Furukawa T,Niwano H,Maruyama S,Narita M,Takizawa J,Satou N,Hashimoto S,Nikkuni K,Toba K,Kishi K,Takahashi M,Aizawa Y,Shibata A: "Comparison of logn-term survival between bone marrow transplantation and maintenance chemotherapy for adult acute lymphoblastic leukemia in first remission." Japanese Journal of Clinical Hematology. 38. 95-99 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kishi K,Takahashi S,Gondo H,Shiobara S,Kanamaru A,Kato S,Hirabayashi N,Moriyama Y,Harada M,Asano S,Hara H,Shibata A: "Second Allogeneic Bone Marrow Transplantation for Posttransplant Leukemia Relapse ; Results of a Survey of Sixty-six Cases in 24 Japanese Institutes." Bone Marrow Transplantation. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suzuki N,Kishi K,Narita M,Furukawa T,Takahashi M,and Aizawa Y: "Dominant appearance of normal hematopoietic progenitors in the adherent layr of long-term marrow culture in chronic myelogenous leukemia-An effect of interferon-a" Niigata Medical Journal. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato N,Kishi K,et al: "Nephrotic syndrome in a bone marrow transplant recipient with chronic graft-versus-host disease." Bone Marrow Transplantation. 16. 303-305 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 瀧澤淳、岸賢治、他: "Fanconi貧血と思われる再生不良性貧血に続発した急性骨髄性白血病に親子間同種骨髄移植を施行した1症例." 臨床血液. 36. 615-620 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岸賢治: "移植後の合併症とその対策、再発とその対策." 血液・腫瘍科. 31. 284-290 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岸賢治、他: "寛解導入療法と骨髄移植における日和見感染症予防の具体的方法とその根拠(新潟大学第一内科一般病棟および無菌室における予防法)" 血液・腫瘍科. 33. 226-231 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] "Second Allogeneic Bone Marrow Transplantation for Post-transplant Leukemia Relapse ; Results of a Survey of Sixty-six Cases in 24 Japanese Institutes." Bone Marrow Transplantation. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 鈴木訓充、岸賢治、他: "慢性骨髄性白血病における骨髄長期培養では正常前駆細胞は付着細胞層に多く存在する -インターフェロンの効果-" 新潟医学会雑誌. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kenji Kishi: "A novel acute promyelocytic leukemia cell line with t(15;17):Differentiation to three types of granulocytes;neutrophil,eosinophil and basophil." Blood. 10. 669a (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] ken Toba: "Classification of cell cycle characterized with DNA/RNA quantitation using 7AAD/PY in hemopoietic malignancy" Experimental Hematology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoaki Sato: "Nephrotic syndrome in a bone marrow transplant recipient with chronic graft‐versus‐host disease" Bone Marrow Transplantation. 16. 303-305 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.Osman,Y.Moriyama: "Enhanced elimination of Ph^T chromosome cells in vitro by combined hyperthermia and other drugs:" Exp Hematol. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Masuhiro,et al.: "Transfection of the bcr/abl oncogene into factor-dependent cells by electroporation" Hematol Oncol. 12. 53-60 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Moriyama,et al.: "Prediction of the ability to purge clonogeric B-cell lymphoma from hurman bone marrow in vitro by heat:" Bone Marrow Transplant. 11. 437-441 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Moriyama,et al.: "Effect of GM-CSF on chemotherapy induced granuloiytopenia in patients with malignancies." AcTa Haematol. 89. 70-75 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Moriyama,et al.: "A simple elimination of clonoglnic Tumor cells from human bone marrow by heat:" Ann Hematol. 64. 266-269 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Moriyama,et al.: "In vitro purging of clonogenic leukimic cells from human bone manow by heat : simulation experiments" Leuk Res. 16. 973-976 (1992)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森山美昭(分担): "血液病学(第2版)" 文光堂, 1813 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 森山美昭(分担): "深在性真菌症の最新治療計画" メディカル:ジャーナル社, 230 (1993)

    • Related Report
      1994 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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