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Analysis of the expression profile of lineage-specific transcription factors in leukemia cells

Research Project

Project/Area Number 07557329
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

HAYASHI Norio  Tohoku University, School of Medicine, Professor, 医学部, 教授 (00004606)

Co-Investigator(Kenkyū-buntansha) FURUYAMA Kazumichi  Tohoku University, School of Medicine, Assistant Professor, 医学部, 助手 (80280874)
MINEGISHI Naoko  University of Tsukuba, Institute of Baseic Medical Sciences, Associate Professor, 基礎医学系, 講師 (40271895)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsGATA-2 / transcription factor / enhancer / promoter / leukemia cells / hematopoiesis / transgenic mouse / GATA-1因子 / GATA-2因子 / 血球分化 / 白血病 / プロモーター / 造血細胞 / トロンボポエチン / MLP / M-TAT細胞 / GATA因子 / 造血前駆細胞 / 病型診断
Research Abstract

The expression of GATA-2 is related to proliferative versus differentiated capability of hematopoietic progenitor cells, and suppression of GATA-2 seems to be essential for hematopoietic differentiation. Therefore, elucidation of the mechanisms controlling GATA-2 expression may offer insight into the earliest aspects of hematopoietic cellular differentiation and may help clarify the mechanisms underlying leukemogenesis, In the present study, we analyzed GATA expression profiles in leukemia cells and also analyzed the regulatory mechanism of GATA-2 gene.
(1) The expression of GATA-2 is closely linked with that of the CD34 antigen in established leukemia cell lines. To ascertain whether the expression profiles of GATA factors are preserved or changed in maligant counterparts of hematopoietic cells, we analyzed primary leukemic blasts from leukemic children, and found a correlation between tumor and respective normal cells in terms of the GATA factors. Namely, in the majority of myelogenou … More s leukemia cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from lymphoblastic leukemia (ALL) patients. GATA-3 mRNA was exressed in all T-ALL cases, but not in any precursor B-ALL.Therefore, exprression analysis of GATA factors may provide a useful tool to determine the lineage commitment of unclassified leukemia.
(2) We isolated and characterized the murine GATA-2 gene, and found that GATA-2 expression is regulated by two distinct promoters. One (IG promoter) is used in general in the tissues and cell lines that express GATA-2. The other promoter (IS promoter) regulates the expression of GATA-2 specifically in hematopoietic cells.
(3) We examined the regulatory activity of the mouse GATA-2 genomic locus in vivo using transgenic mice. Trans genes containing about 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of BETA-galactosidase reporter gene specifically to the para-aortic splanchnopleula, aorta-ganad-mesonephros region and in the neural tissues, In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenaous expression profiles of GATA-2 in these tissues. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Minegishi, Naoko: "Alternative promoters regulate transcription of the mouse GATA-2 gene." J.Biol.Chem.273. 3625-3634 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, Satoru: "Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene." J.Biol.Chem.272. 12611-12615 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onodera, Ko: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 94. 4487-4492 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onodera, Ko: "Conserved structure, regulatory elements, and transcriptional regulation from the GATA-1 gene testis promoter." J.Biochem.(Tokyo). 121. 251-263 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minegishi, Naoko: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells." Int.J.Hematol.65. 239-247 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minegishi, N., Ohta, J., Suwabe, N., Nakauchi, H., Ishihara, H., Hayashi, N., Yamamoto, M.: "Alternative promoters regulate transcription of the mouse GATA-2 gene." J.Biol.Chem.273. 3625-3634 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takahashi, S., Onodera, K., Motohashi, H., Suwabe, N., Hayashi, N., Yanai, N., Nabesima, Y., Yamamoto, M.: "Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene." J.Biol.Chem.272. 12611-12615 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onodera, K., Takahashi, S., Nishimura, S., Ohta, J., Motohashi, H., Yomogida, K., Hayashi N., Engel, J.D.Yamamoto, M.: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 94. 4487-4492 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Onodera, K., Yomogida, K., Suwabe, N., Takahashi, S., Muraosa, Y., Hayashi, N., Ito, E., Gu, L., Rassoulzadegan, M., Engel, J.D., Yamamoto, M.: "Conserved structure, regulatory elements, and transcriptional regulation from the GATA-1 gene testis promoter." J.Biochem.(Tokyo). 121. 251-263 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minegishi, N., Morita, S., Minegishi, M., Tsuchiya, S., Konno, T., Hayashi, N., Yamamoto, M.: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells." Int.J.Hematol.65. 239-249 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Minegishi, Naoko: "Alternative promoters regulate transcription of the mouse GATA-2 gene" J.Biol.Chem.273・6. 3625-3634 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagai, Tadashi: "Regulation of NF-E2 activity in erythroleukemia cell differentiation" J.Biol.Chem.273・9. 5358-5365 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Minegishi, Naoko: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells" Int.J.Hematol.65・3. 239-249 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagai, Tadashi: "5-aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line" J.Biochem.(Tokyo). 121・3. 487-495 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi, Satoru: "Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene." J.Biol.Chem.272・19. 12611-12615 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Onodera, Ko: "GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis." Proc.Natl.Acad.Sci.USA. 94・9. 4487-4492 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oydaka, Tatsuya: "Bach proteins belong to a novel family of BTB-basic leucine zipper transcription factors that interact with MafK and regulate transcription through the NF-E2 site" Mol. Cell. Biol.16・11. 6083-6095 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Onodera, Ko: "Comserved structure, regulatory elements, and transcriptional regulation from the GATA-1 gene testis promoter" J. Biochem. 121・2. 251-263 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagai, Tadashi: "5-Aminolevulinate synthase expression and hemoglobin synthesis in a human myelogenous leukemia cell line" J. Biochem.121・3. 487-495 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Minegishi, Naoko: "Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells" Int. J. Hematol. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagai, Mayumi: "Novel regulation of σ-aminolevulinate synthase in the rat Harderian gland" Biochem. Pharmacol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Furuyama, Kazumichi: "Peridoxine refractory X-linked sideroblastic anemia cused by a point mutation in the erythroid 5-aminolevulinate synthase gene" Blood. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 五十嵐 和彦: "Conditional expression of the ubiguitous transcription factor Mafk induces erythroleukemia cell differentiation" Proc. Natl. Acad. Sci. USA. 92. 7445-7449 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 五十嵐 和彦: "Activity and expression of murine small Maf family protein Mafk" J. Biol. Chem.270. 7615-7624 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 伊東 健: "Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins" Mol. Cell. Biol.15. 4184-4193 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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