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1999 Fiscal Year Final Research Report Summary

Molecular mechanism of hematopoietic regulation by leukemia-related transcription factor AML1(PEBP2αB)

Research Project

Project/Area Number 10670961
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

OKUDA Tsukasa  Kyoto Prefectural University of Medicine, Department of Hygiene, Assistant Professor (Kohshi), 医学部, 講師 (30291587)

Project Period (FY) 1998 – 1999
KeywordsAML1 / PEBP2 / leukemia / hematopoiesis / transcription / embryonic stem(ES) cell / oncogene / gene targeting
Research Abstract

We analyzed the molecular mechanism of actions played by leukemia-related transcription factor, AML1(PEBP2αB), on hematopoietic regulation by using an in vitro experimental system, which was newly established through this research project. Our results are summarized as follows :
1. We established an in vitro experimental system by using murine embryonic stem(ES) cell differentiation, through which the in vivo hematological phenotype observed in the AML1-deficient animals could be replicated in vitro.
2. The hematopoietic defect resulting from homozygous null allele for AML1 could be rescued by re-expressing wild-type AML1 cDNA, indicating compelling evidence that the AML1-knockout phenotype is due solely to the lack of this gene.
3. This rescue was observed in vivo in that the rescue clones contribute to lympho-hematopoiesis in chimera mice.
4. The rescue required the transactivation domain of AML1 molecule.
5. Forced expression of the same AML1 cDNA did not rescue the hematopoietic defect, suggesting that transcriptional control of AML1 was important for the biologic activity of the PEBP2 transcription complex. Consistent with this observation, the expression level of AML1 fluctuated as ES cells differentiated in vitro.
6. We analyzed the expression of the known AML1-target genes and found that most of them were retained even in the absence of the active AML1 molecule. Therefore, it is suggested that as yet un-identified transcriptional target(s) exists which mediates AML1's biologic activities.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Okuda, T.: "Biological characteristics of the leukemia-associated transcriptional factor AML1 disclosed by hematopoietic rescue of AML1-deficient embryonic stem cells by using a knock-in strategy"Molecular and Cellular Biology. 20. 319-328 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 奥田 司: "AML1と白血病"血液腫瘍科. 40. 1-12 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 奥田 司: "AML1遺伝子操作マウス"医学のあゆみ. 190. 323-329 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 奥田 司: "造血初期発生制御における転写いんしAML1の役割"実験医学. 17. 1136-1143 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 奥田 司: "AML1遺伝子の生物学的意義"現代医学. 31. 125-1134 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuda, T.: "Role of AML1 in normal and leukemic hematopoiesis. In "Molecular Target for Hematological Maligancies and Cancer" (Ed. by Niho Y.)"Kyushu University Press(Fukuoka, Japan)(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuda T., Takeda K., Fujita Y. Nishimura M., Yagyu S., Yoshida M.,Akira S., Downing J.R. and Abe T.: "Biological characteristics of the leukemia-associated transcriptional factor AML1 disclosed by hematopoietic rescue of AML1-deficient embryonic stem cells by using a knock-in strategy."Molecular and Cellular Biology. 20(1). 319-328 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuda T., Fujita Y., Nishimura M., Downing J.R., and Abe T.: "Role of AML1 in normal and leukemic hematopoiesis. In "Molecular Target for Hematological Malignancies and Cancer" (ed.by Niho Y.)"Kyushu University Press (Fukuoka,Japan). in press. (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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