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Apoptosis in Human leukemia and Preleukemia

Research Project

Project/Area Number 08457276
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YOSHIDA Yataro  KYOTO UNIVERSITY Center for South East Asian Studies Division of Human Environment, Professor, 東南アジア研究センター, 教授 (80064525)

Co-Investigator(Kenkyū-buntansha) SASADA Masataka  KYOTO UNIVERSITY College of Medical Technology, Division of Medical Technology,, 医療短期大学部, 教授 (30144364)
OGUMA Shigeru  KYOTO UNIVERSITY Department of Hematology/Oncology, Graduate School of Medicine,, 医学研究科, 助手 (00169260)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Keywordsapoptosis / endonuclease / human leukemia and preleukemia / hematopoietic cell differentiation / 白血病 / 前白血病 / 細胞増殖と細胞死
Research Abstract

1.We have isolated Mg2+/Mn2+-dependent endonuclease activies from nuclear aswell as cytoplasm of human myeloid leukemia cells. The former had a molecular size of 30kD, while that of the latter was 130-140kD, indicating a dimer form in the cytoplasm. Both are capable of producing nucleosomal-size DNA fragmentation when added to DEPC-treated nuclei as substrate. The cleavage pattern of 3'-OH and 5'-P, inhibition by known inhibitors of apoptosis suggest their participation in apoptotic process.
2.Hematopoietic cells contain at least three types of endonucleases distinct from each other in cation dependency and inhibition by distinct agents. The stem cells, and immature blast cells from leukemia and preleukemia have a high activity for Mg2+/Mn2+-dependent endonuclease. Differentiation is associated with a decrease of this enzyme and generally with emergence of new types of endonuclease activities, i. e., Mg2+/Ca2+-dependent and acidic endonucleases. Differentiation experiment of leukemia and preleukemia cells indicate that susceptibility to apoptosis is not concomitant with cell differentiation. Thus, apoptosis apparently is a cellular event distinct from differentiation.
3.The pulse field method is useful in studing the early biochemical events preceding the nucleosomal-size DNA fragmentation, which is a well-known parameter for apoptosis as the laddering. We could dissect the processes in DNA cleavage taking place early following the etoposide treatment of human leukemia cells. We could demonstrate a sequential cleavage of DNA from a huge size (2-5 Mb) DNA cleavage down to less than 50 Kb DNA fragments. Dichloroisocoumarine can specifically inhibit both apoptotic morphology and less than 50 Kb DNA fragments which is in the size range seen in DNA laddering.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Anzai N, et al.: "Ca2+/Mg2+-dependment endonuclease in marrow CD34 positive and erythrroidcells in myelodysplasia." Leukemia Res. 21. 731-734 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Anzai N, et al.: "Distribution of endogenous endonuclease activities capable of producing internucleosomal DNA cleavage in hematopoietic cells." Int J Haematol. 66. 387-390 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawabata H, et al.: "High levels of Ca2+-independent endonuclease activity capable of producing nucleosomal-size DNA fragmetation in non-adherent marrow mononuclear cell nuclei from patients with myelodysplastic syndromes and acute myeloid leukemia." Leukemia. 10. 67-73 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kawabata H, et al.: "Mg2+ or Mn2+ -dependent endonuclease activities of human myeloid leukemia cells capable of producing nucleosoma-size DNA fragmentation." Biochem Biophys Res Com^1. 233. 133-138 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshida Y, et al.: "Apoptosis in normal and neoplastic hematopoiesis." Crit Rev Oncol/Hematol. 24. 185-211 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshida Y, et al.: "Apoptosis as a cell biological abnormality in myelodysplasia." Path Biol. 45. 473-578 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Kawabata, N.Anzai, Y.Ueda, H.Masutani, T.Hirama, Y.Yoshida and M.Okuma: "High levels of Ca^<2+> -independent endonuclease activity capable of producing nucleosomal-size DNA fragmentation in non-adherent marrow mononuclear cells from patients with myelodysplastic syndromes and acute myelogenous leukemia." Leukemia. 10. 67-73 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Yoshida: "Treatment of the myelodysplastic syndromes : An updated Japanese experience." Seminars in Hematology. 33(3). 246-255 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Yoshida, H.Kawabata, N.Anzai and K.Tohyama: "Apoptosis as a cell biological abnormality in myelodysplasia." Pathologie Biologie. 45(7). 573-578 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Yoshida, N.Anzai, H.Kawabata: "Apoptosis in normal and neoplastic hematopoiesis." Critical Reviews in Oncology/Hematology. 24(3). 185-211 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Ido, C.Nagata, N.Kawakami, H.Shimizu, Y.Yoshida, T.Nomura and H.Mizoguchi: "A case-control study of myelodysplastic syndromes among Japanese men and woman." Leukemia Research. 20(9). 727-731 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Shiga, T.Furukawa, I.Koyanagi, M.Yamagishi, Y.Yoshida, T.Takahashi, R.Kannagi and T.Mori: "Laboratory diagnosis of anemia and related diseases using multivariate analysis." American Journal of Hematology. 54. 108-117 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Oguma, Y.Yoshida, M.Okuma, H.Uchino, T.Maekawa, T.Nomura, H.Mizoguchi and The Refractory Anemia Study Group of The Ministry of Health and Welfare, Japan.: "Mode of disease progression in primary myelodysplastic syndromes : A Japanese Co-operative study." Leukemia Research. 21(3). 241-247 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Kawabata, N.Anzai, H.Masutani, T.Hirama, T.Hishita, M.Dodo, T.Masuda, Y.Yoshida and M.Okuma: "Mg^<2+> -or Mn^<2+> -Dependent Endonuclease activities of human myeloid leukemia cells capable of producing nucleosomal-size DNA fragmentation." Biochemical and Biophysical Research Communications. 233. 133-138 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Tohyama, H.Tsutani, Y.Wano, H.Iwasaki, T.Fukushima, Y.Urasaki, Y.Kawai, T.Nakamura, Y.Yoshida, T.Ueda: "Anti-leukemia chemotherapy of high-risk myelodysplastic syndromes." The Oncologist. 2. 160-163 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Yoshida: "Apoptosis as a parameter of cytokine treatment in myelodysplasia." Leukiema Research. 21(5). 427-428 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Anzai, H.Kawabata, T.Hishita, Y.Yoshida, Y.Ueda and M.Okuma: "CA^<2+>/MG^<2+>-Dependent Endonuclease in marrow CD34 positive and erythroid cells in myelodysplasia." Leukemia Research. 21(8). 731-734 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Anzai, H.Kawabata, T.Hishita, M.Dodo, K.Tohyama, H.Masutani, Y.Yoshida: "Distribution of endogeneous endonuclease activities capable of producing internucleosomal DNA cleavage in hematopoietic cells." International Journal of Hematology. 66(3). 387-390 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Anzai N, et al.: "Ca2+/Mg2+-dependent endonuclease in marrow CD34 positive and erythroid cells in myelodysplasia." Leukemia Res. 21. 731-734 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Anzai N, et al.: "Distribution of endogenous endonuclease activities capable of producing internucleosomal DNA cleavage in hematopoietic cells." Int J Haematol. 66. 387-390 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawabata H, et al.: "High levels of Ga2+-independent endonuclease activity capable of producing nucleosomal-size DNA fragmentation in non-adherent marrow mononuclear cell nuclei from patients with myelodysplastic syndromes and acute myeloid leukemia." Leukemia. 10. 67-73 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawabata H, et al.: "Mg2+ or Mn2+ -dependent endonuclease activities of human myeloid leukemia cells capable of producing nucleosoma-size DNA fragmentation." Biochem Biophys Res Com. 233. 133-138 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida Y, et al.: "Apoptosis in normal and neoplastic hematopoiesis." Crit Rev Oncol/Hematol. 24. 185-211 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida Y, et al.: "Apoptosis as a cell biological abnormality in myelodysplasia." Path Biol. 45. 473-578 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Ido,C.Nagata.,Y.Yoshida,et al.: "A case-control study of myelodysplastic syndromes among Japanese men and women." Leukemia Research. 20(9). 727-731 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Tominaga,Y.Yoshida, et al.: "Crohn's disease limited to the terminal ileum in a patient with myelodysplastic syndrome (Refractory Anemia)." Jpn Arch Int Med. 43(3). 51-56 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshida: "The FAB classification of acute leukemias." Asian Medical Journal. 39(10). 507-512 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshida,N.Anzai,H.Kawabata: "Apoptosis in nermal and neoplastic hematopoiesis." Critical Reviews in Oncology/Hematology. 24(3). 185-211 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshida: "Treatment of the myelodysplastic syndromes : An updated Japanese experience." Seminars in Hematology. 33(3). 246-255 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Kawabata,N.Anzai,Y.Yoshida,et al.: "High levels of Ca2+-independent endonuclease activity capable of producing mueleosomal-size DNA fragmentation in non-adherent marrow mononuclear cells from patients with myelodysplastic syndromes and acute mylogenous leulemia." Leukemia. 10. 67-73 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Yoshida,R.Ohno and K.Kimura: "A phase II clinical trial of cytarabine ocfosfate in acute leukemia and myelodysplastic syndromes Differentiation Therapy 〈Challenges of Medicine Volume 10〉" Samuel Waxman Ares-Serono Symposia Publications, (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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