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Role of BMI-1 in leukemia

Research Project

Project/Area Number 16590931
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Cancer Center (2005)
Nagoya University (2004)

Principal Investigator

YAMAMOTO Kauzhito  Aichi Cancer Center, Molecular Medicine, Researcher, 遺伝子医療研究部, 研究員 (60250247)

Co-Investigator(Kenkyū-buntansha) NAOE Tomoki  Nagoya Univ Grad Scl Med, Hematol and Med Oncol, Professor, 大学院・医学系研究科, 教授 (50217634)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsBMI-1 / Differentiation / Proliferation / Apoptosis / Mouse model / 造血幹細胞
Research Abstract

Recent studies have suggested that one of the polycomb group genes, BMI-1,has an important role in the maintenance of normal and leukemia stem cells by repressing the INK4a/ARF locus. Firstly, we quantitatively examined the BMI-1 expression level in acute myeloid leukemia (AML) cells. The BMI-1 expression level of AML samples was significantly higher than that of normal bone marrow controls. The CD34-positive fraction of cord blood showed a transcript about 8 times as high as CD34-negative fraction, whereas normal peripheral mononuclear cells showed a moderate transcript, lower than a cell line expressing a high BMI-1 level. According to FAB classification, BMI-1 transcript of M0-type was about 3 times higher than that of other types of AMLs. The INK4a-ARF transcript had a tendency of inverse proportion to that of BMI-1. This suggested that BMI-1 in part downregulates the transcript of INK4a-ARF locus in leukemia. In an M0 patient with a high transcript of BMI-1,the level fell promptly … More and maintained a low value after achieving complete remission. Secondly, to investigate the role of BMI-1 in proliferation, differentiation and apoptosis of leukemias, 32D cells were infected with MIG-BMI-1-IRES-EGFP vector or MIG vector, and the GFP positive rates of BMI-1 overexpressing 32D cells gradually increased under IL-3 diminished conditions, and the consecutive MTT assays using cells sorted by GFP positivity confirmed this finding, suggesting that BMI-1 could confer growth advantages on 32D cells under IL-3 diminished conditions. Exposure of the GFP sorted 32D cells to G-CSF revealed that BMI-1 overexpression suppressed the granulocytic differentiation of 32D cells by G-CSF. The expressions of CD11b and Gr-1 were both suppressed by the overexpression of BMI-1,and real-time PCR analyses indicated that the expression levels of MPO was remarkably suppressed, while those of C/EBPα were not significantly changed. These results revealed that BMI-1 delayed granulocytic differentiation and ameliorated the growth of 32D cells under IL-3 diminished conditions. We also established a stroma-dependent AML (M0) cell line which overexpresses BMI-1. This line is a useful cell line to study biology of leukemia cells overexpressing BMI-1. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2005 Other

All Journal Article (5 results)

  • [Journal Article] BMI-1 is highly expressed in M0-subtype acute myeloid leukemia2005

    • Author(s)
      Sawa M
    • Journal Title

      Int J Hematol. 82・1

      Pages: 42-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] BMI-1 is highly expressed in M0-subtype acute myeloid leukemia2005

    • Author(s)
      Sawa M et al.
    • Journal Title

      Int J Hematol 82

      Pages: 42-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Establishment of a stroma-dependent myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene.

    • Author(s)
      Ninomiya M
    • Journal Title

      Cancer Genetics and Cytogenetics (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Establishment of astroma-dependent myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene.

    • Author(s)
      Ninomiya M et al.
    • Journal Title

      Cancer Genetics and Cytogenetics (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Establishment of a stroma-dependent myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene.

    • Author(s)
      Ninomiya M
    • Journal Title

      Cancer Genetics and Cytogenetics (In press)

    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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