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Expression of c-abl gene and it's coded protein in Piladelphia chromosome (Ph^1)

Research Project

Project/Area Number 62570531
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionHokkaido University

Principal Investigator

OKABE Mihiro  Hokkaido University Medical Hospital, 医学部付属病院, 助手 (40113534)

Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsPhiladelphia chromosome(Ph^1) / CML / Ph^1 positive ALL / C-abl gene / Bcr rearrangement / Bcr-abl hybrid mRNA / Tyrosine kinase / チロシンキナーゼ / N-ras遺伝子 / Philadelphia染色体(Ph^1) / CML:Ph^1陽性ALL / Bcr再構成 / Bcr-abl hybridmRNA / チロニンキナーゼ / Ph染色体 / abl遺伝子 / bcr再構成 / transforming遺伝子
Research Abstract

Molecular analyses of bcr and abl genes and transforming genes have been carried out in Philadelphia chromosone(Ph^1)-positive leukemia. Southern blot analysis of bcr rearrangement demostrated that all CML cases have breakpoints culustered on introns among either bcr exson 2, 3 or 4. On the other hand, Ph^1-positive ALL cases showed heterogenity of chromosome 22g 21 breakpoints, with half of the cases showing no bcr rearrangement. Northern blot analysis of polyadenylated RNA showed approximately 8.5-kb bcr-abl hybrid mRNA in CML cases. In 2 Ph^1-positive ALL cases with no bcr rearrangement (Ph^<1+>, bcr^- ALL), the novel abl mRNA were seen in the position of approximately 7.5-kb and 7.3-kb respectively, but signal of mRNA was not seen in that position by Norther blot with bcr cDNA probe that contained bcr exson 1 and a part of exson 2. These results are compatible to Herrmans's report that in Ph^<1+> bcr^- ALL the breskpoints are present within the intron between the bcr gene exson 1 a … More nd 2 at least 40-kb upstream of the bcr lows. Ph^1-positive ALL cells showed the phenotypical and genotypical character as Pro-B cells. However, in Ph^<1+>, bcr^- ALL cases, one case had simultaneous proliferation of the lymphoid blasts and myeloblast and the leukemic cells of other one case showed the myeloid defferentiation in vitro, thus suggesting that P190 abl kinase, supeculated to be specific to Ph^<1+> bcr^- ALL play a role in the proliferation of myeloid cells and further may be associated with aute process rather than chronic process in ltukemogenesis. The tyrosine kinase activity of CML cells and Ph^<1+>, bcr^- ALL cells were augmented in cytozol fraction, different from other types of leukemias. This result may be related to the membrane-phobic character of P210 bcr-abl kinase. Furthermore, we have analyzed the genetic events in transformation to blast crisis from CML in chronic phase. No obvious difference was not seen between the breakpoints within bcr and the transformation to crisis. CML in crisis showed the augmented expression of 8.5-kb bcr-abl mRNA when compared with those in chrnoc phase. in DNA transfection assay using N1H3T3 cells, activated N-ras genes were detected in 2 of 7 cases of CML in crisis. These results suggest that in addition to augementation of abl gene expression, active transforming genes including ras family genes may plat an important role in giving rise to gransformation to blast crisis. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Mihiro Okabe,et al: Blood. 69. 990-998 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe,it al: Tohoku J Exp Med. 152. 197-207 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe,et al: Acta Haematologica Jpn. 51. 1471-1480 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe,et al: BLut. in puss. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 岡部實裕 他: 日本臨床. 45. 91-98 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 岡部實裕 他: 日本臨床. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 岡部實裕 他: "白血病細胞の生物学、医学的特性とその制御、philaclelphia染色体陽性急性リンパ芽球性白血病におけるbcr再構成およびbcr,abl遺伝子" 癌と化学療法社, 175-183 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 岡部實裕 他: "白血病の新しい診断技術-分類と最近の問題点Ph^1陽性白血病におけるbcrとc-abl遺伝子" 医葉薬出版社, 156-160 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe, et al.: "Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia Chromosome-positive acute lymphocytic leukemia." Blood. 69. 990-998 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe, et al.: "Non-T, non-B acute lymphocytic leukemia : Cellular origin based on molecular analyses of immunoglobulin and T-cell - and -chain receptor gene rearrangement." Tohoku J. Exp. Med.152. 197-207 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe, et al.: "Philadelphia Chromosome-positive leukemia : Molecular analysis of bcr and abl genes and transforming genes." Acta Haematologica Jpn.51. 1471-1480 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro Okabe, et al.: "bcr Rearrangement and c-abl gene expression with simultaneous proliferation of lymphoid and myeloid blasts." Blut. in press. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Mihiro,Okabe etal.: Blood. 69. 990-998 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mihiro,Okabe etal.: Tohoku J Exp Meol. 152. 197-207 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mihiro,Okabe etal.: Acta Haematologica Jpn. 51. 1471-1480 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Mihiro,Okabe etal.: BLnt. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡部實裕 他: 日本臨床. 45. 91-98 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡部實裕 他: 日本臨床. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡部實裕 他: "白血病細胞の生物学、医学的特性とその制御、Philadelphia染色体陽性急性リンパ芽球性白血病におけるbcr再構成およびbcr、abl遺伝子" 癌と化学療法社, 175-183 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡部實裕 他: "白血病の新しい診断技術-分類と最近の問題点 Ph^1陽性白血病におけるbcrとc-abl遺伝子" 医歯薬出版社, 156-160 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] 岡部實裕 他: 日本臨床. 45. 2843-2850 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mihiro OKABE, et al: Tohoku J. exp. Med.152. 197-207 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mihiro OKABE,et al: Blood. 69. 990-998 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 宮崎保(監修),岡部實裕: "「白血病細胞の生物学題特性とその制御」 -Philadelphia 染色体陽性急性リンパ芽球性白血病におけるbcr再構成およびbcr,abl遺伝子の発現" 癌と化学療法社, 453 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 岡部 實裕: "新潟シンポジウムー白血病の最新の分類と問題点-"

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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