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Roles of GATA-2/retinoic acid receptor pathways and TEL-AML1 translocation in leukemia

Research Project

Project/Area Number 15591037
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAichi Cancer Center

Principal Investigator

TSUZUKI Shinobu  Aichi Cancer Center, Division of Molecular Medicine, Senior Researcher, 遺伝子医療研究部, 主任研究員 (00342965)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsGATA-2 / retinoic acid receptor / leukemia / TEL-AML1 / pro-B cells
Research Abstract

(1)Although abnormal retinoic acid receptors are known to cause leukemia, the mechanisms thereby are not clear. We have found retinoic acid receptors are capable of binding to transcription factor GATA-2,and through this interaction GATA-2 functions are rendered responsible to retinoic acid. These findings suggest that retinoic acid exert its action, in addition to canonical receptors, via GATA-2 factor that are normally expressed in immature hematopoietic cells. Indeed, we were able to show that colony formation activities of hematopoietic cells are affected by retinoic acid. Leukemia-associated abnormal retinoic acid receptors may disrupt normal GATA-2 functions, thus leading to leukemia.
(2)TEL-AML1 is a fusion gene generated as a result of t(12;21) chromosomal translocation, and the commonest genetic abnormality in child acute lymphocytic leukemia. This translocation is linked to pro-B cell leukemia, but the molecular mechanisms involved are not clear. We have modeled the TEL-AML1 translocation in mice and analyzed its function. The mice were found to have relative accumulation of pro-B cells at the expense of more differentiated stages of B cells, thus providing evidence that TEL-AML1 fusion gene product is capable of inhibiting B cell differentiation program. More detailed analysis is currently conducted.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (11 results)

All 2004 Other

All Journal Article (9 results) Publications (2 results)

  • [Journal Article] Modeling‘first hit' functions of the t(12;21) TEL-AML1 translocation in mice.2004

    • Author(s)
      Tsuzuki S, Seto M, Greaves M, Enver T
    • Journal Title

      Proc Natl Acad Sci U S A. 101(22)

      Pages: 8443-8448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Crosstalk between retinoic acid signaling and transcription factor GATA-2.2004

    • Author(s)
      Tsuzuki S, Kitajima K, Nakano T, Glasow A, Zelent A, Enver T
    • Journal Title

      Mol Cell Biol. 24(15)

      Pages: 6824-6836

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Identification and characterization of a novel gene, C13orf25, as target 13q31-q32 amplification in malignant lymphoma.2004

    • Author(s)
      Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M.
    • Journal Title

      Cancer Res. 64(9)

      Pages: 3087-3095

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Genome-wide array-based comparative genomic hybridization of diffuse large B-cell lymphoma : comparison between CD5-positive and CD5-negative cases.2004

    • Author(s)
      Tagawa H, Tsuzuki S, Suzuki R, Karnan S, Ota A, Kameoka Y, Suguro M, Matsuo K, Yamaguchi M, Okamoto M, Morishima Y, Nakamura S, Seto M.
    • Journal Title

      Cancer Res. 64(17)

      Pages: 5948-5955

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma.2004

    • Author(s)
      Kameoka Y, Tagawa H, Tsuzuki S, Karnan S, Ota A, Suguro M, Suzuki R, Yamaguchi M, Morishima Y, Nakamura S, Seto M.
    • Journal Title

      Oncogene 23(56)

      Pages: 9148-9154

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Modeling ‘first hit' functions of the t(12;21) TEL-AML1 translocation in mice.2004

    • Author(s)
      Tsuzuki S, Seto M, Greaves M, Enver T
    • Journal Title

      Proc Natl Acad Sci USA. 101(22)

      Pages: 8443-8448

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Identification and characterization of a novel gene, C13orf25,as a target for 13q31-q32 amplification in malignant lymphoma.2004

    • Author(s)
      Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M.
    • Journal Title

      Cancer Res. 64(9)

      Pages: 3087-3095

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Modeling ‘first hit' functions of the t(12;21) TEL-AML1 translocation in mice.2004

    • Author(s)
      Tsuzuki S, Seto M, Greaves M, Enver T
    • Journal Title

      Proc Natl Acad Sci U S A. 101(22)

      Pages: 8443-8448

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma.2004

    • Author(s)
      Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M.
    • Journal Title

      Cancer Res. 64(9)

      Pages: 3087-3095

    • Related Report
      2004 Annual Research Report
  • [Publications] Tsuzuki S, Seto M, Greaves M, Enver T: "Modelling 'first hit'functions of the t(12,21) TEL-AML1 translocation in mice."Proc.Natl.Acad.Sci.USA. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuzuki S, Kitajima K, Nakano T, Glasow A., Zelent A, Enver T: "Crosstalk between retinoic acid signaling and transcription factor GATA-2."Molecular and Cellular Biology. (in press).

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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