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Investigation of mechanism(s) underlying blast crisis of chronic myelogenous leukemia (CML) and analysis of genes involved in blast crisis of CML

Research Project

Project/Area Number 14370304
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HONDA Hiroaki  Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (40245064)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 2003: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2002: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsCML / p210BCR / ABL / transgenic mice / blast crisis / BXH2 / BHX2
Research Abstract

Chronic myelogenous leukemia (CML) is a clonal disorder of hematopoietic stem cells transformed by p210BCR/ABL, characterized by excessive and uncontrolled proliferation of myeloid cells. Clinically it begins as an indolent chronic phase, but inevitably accelerates and finally progresses into a fatal blast crisis, which resembles acute leukemia. Although additional genetic change(s) is considered to contribute to the blast crisis of CML, underlying molecular mechanism(s) has remained unclear.
We have developed transgenic mice expressing p210BCR/ABL using a promoter of a gene preferentially expressed in hematopoietic precursor cells. The transgenic mice reproducibly exhibited a myeloproliferative disorder closely resembling human CML, allowing us to consider that the transgenic mice to be an excellent animal model for human CML. Using this transgenic model as a tool, we have been attempting to identify genes responsible for progression of CML. To this aim, we did "in vivo mutagenesis" by infecting retroviruses into CML transgenic mice. BHX2, a mouse strain which transmits retroviruses through milk (Nature Genet. 23, 348-53, 1999), is used for this study. We crossmated p210BCR/ABL transgenic mice with BXH2 mice and backcrossed the mice to BXH2 for three times to have BXH2 genetic background. We have been examining the cell count and cell smear of pheripheral blood of the mice. So far, we have found 3 mice that developed acute leukemia. We will continue this study and when we have enough number of mice that exhibited acute leukemia, we isolate DNA from leukemic samples and identify genes responsible for blast crisis of CML by PCR using virus-specific primers.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kuribara R.: "Pivotal roles of Bim, a proapoptotic relative of Bcl-2, in the leukemogenesis of chronic myeloid leukemia."Molecular and Cellular Biology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inokuchi K.: "Novel transgenic mice expressing P230 Bcr/Abl developed myeloproliferative disorder : longer disease latency, thrombocytosis and mild leukocytosis."Blood. 102. 320-323 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki K.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes."Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Huang J.: "Differential regulation of cell migration, actin stress fiber organization and cell transformation by functional domains of Cas."Journal of Biological Chemistry. 277. 27265-27272 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yi J.: "Members of the zyxin family of LIM proteins interact with members of the p130cas family of signal transducers."Journal of Biological Chemistry. 277. 958-9589 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamoto T.: "Analysis of gene expression profile in p130(Cas)-deficient fibroblasts."Biochemical and Biophysical Research Communication. 194. 635-641 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuribara R.: "Pivotal roles of Bim, a proapoptotic relative of Bcl-2, in the leukemogenesis of chronic mycloid leukemia"Mol. Cell. Biol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inokuchi K.: "Novel tiansgenic mice expressing P230 Bcr/Abl developed myeloproliferative disor der : longer disease latency, thrombocytosis and mild leukocytosis"Blood. vol.102. 320-323 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki K.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes"J. Biol. Chem.. vol.277. 47014-47021 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Huang J.: "Differential regulation of cell migration, actin stress fiber organization and cell transformation by functional domains of Cas"J. Biol. Chem.. vol.277. 27265-27272 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yi J.: "Members of the zyxin family of LIM proteins interact with members of the p130cas family of signal transducers"J. Biol. Chem.. vol.277. 9580-9589 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamoto T.: "Analysis of gene expression profile in p130(Cas)-deficient fibroblasts"Biochem. Biophys. Res. Commn.. vol.194. 635-641 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuribara R.: "Pivotal roles of Bim, a proapoptotic relative of Bcl-2, in the leukemogenesis of chronic myeloid leukemia"Molecular and Cellular Biology. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Inokuchi K.: "Novel transgenic mice expressing P230 Bcr/Abl developed myeloproliferative disorder : longer disease latency, thrombocytosis and mild leukocytosis"Blood. 102. 320-323 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyazaki K.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes"Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Huang J.: "Differential regulation of cell migration, actin stress fiber organization and cell transformation by functional domains of Cas"Journal of Biological Chemistry. 277. 27265-27272 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yi J.: "Members of the zyxin family of LIM proteins interact with members of the p130cas family of signal transducers"Journal of Biological Chemistry. 277. 9580-9589 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamoto T.: "Analysis of gene expression profile in p130(Cas)-deficient fibroblasts"Biochemical and Biophysical Research Communication. 194. 635-641 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyazaki K.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes"Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Huang J.: "Differential regulation of cell migration, actin stress fiber organization and cell transformation by functional domains of Cas"Journal of Biological Chemistry. 277. 27265-27272 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yi J.: "Members of the zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers"Journal of Biological Chemistry. 277. 9580-9589 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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