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Identification of the downstream target genes regulated by MUM1/IRF4 and its application for the novel molecular targeting therapy in lymphoid malignancies

Research Project

Project/Area Number 16590953
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

IIDA Shinsuke  Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (50295614)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMUM1 / IRF4 / lymphoid makignancies / transcriptional regulation genes / molecular targeting therapy / MIG / CXCR3 / B-CLL / DLBCL / B細胞 / 転写調節 / 多発性骨髄腫 / びまん性大細胞型リンパ腫 / 慢性リンパ性白血病 / び慢性大細胞型リンパ腫 / FKBP3
Research Abstract

MUM1(multiple myeloma oncogene 1)/IRF4(interferon regulatory factor 4) is a transcription factor that is activated as a result of t(6;14)(p25;q32) in multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which proliferated at a higher rate than the parental cells, and performed cDNA microarray analysis to identify genes whose expression is regulated by MUM1. We found that the expression of four genes including FK506-binding protein 3(FKBP3), the Monokine induced by interferon-g(MIG), Fas apoptotic inhibitory molecule(Faim) and Zinc finger protein 94 was altered in the MUM1-expressing cells. We then focused on MIG since its expression was immediately upregulated by MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with PU.1, and the interaction between MUM1 and the MIG promoter sequence was confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell lines, and treatment with neutralizing antibodies against MIG and its receptor, CXCR3, partially inhibited the proliferation of two MUM1-expressing lines. These results suggest that MUM1 plays roles in the progression of B-cell lymphoma/leukemia by regulating the expression of various genes including MIG. The MIG expression in the diffuse large B-cell lymphoma-derived cell lines was also seen in those expressing highly amount of the MUM1. We then used Affymetrix GeneChip assay to search for differentially expressed genes in between a Burkitt's lymphoma-derived cell line, P3HR-1 transfected with MUM1 and that transfected with empty vector alone. We have so far identified forty-four upregulated and twenty-two downregulated genes in MUM1-expressing cells, which are being explored for their roles in B-cell tumorigenesis.

Report

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

    (33 results)

All 2005 2004

All Journal Article (33 results)

  • [Journal Article] Anti-tumor effect of a novel IKK-β inhibitor on multiple myeloma.2005

    • Author(s)
      Sanda T, Iida S, et al.
    • Journal Title

      Clin Cancer Res 11

      Pages: 1974-1982

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CC Chemokine receptor 4 (CCR4) positive diffuse large B-cell lymphoma involving the skin : A case report.2005

    • Author(s)
      Ishida T, Iida S, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 148-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-myeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis.2005

    • Author(s)
      Sanda T, Iida S, et al.
    • Journal Title

      Leukemia 19

      Pages: 901-909

    • 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] Global real-time quantification/reverse transcription-polymerase chain reaction detecting protooncogenes associated with 14q32 chromosomal translocation in multiple myeloma.2005

    • Author(s)
      Tajima E, Iida S, et al.
    • Journal Title

      Haematologica/The Hematol J 90(4)

      Pages: 559-562

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of the API2-MALT1 fusion transcript in cytological specimens of the patients with pulmonary MALT lymphoma.2005

    • Author(s)
      Inagaki H, Iida S, et al.
    • Journal Title

      Int J Hematol 82

      Pages: 59-62

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple myeloma oncogene 1(MUM1)/interferon regulatory factor 4(IRF4) upregulates monokine induced by interferon-gamma(MIG) gene expression in B-cell malignancy.2005

    • Author(s)
      Uranishi M, Iida S, et al.
    • Journal Title

      Leukemia 19

      Pages: 1471-1478

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ark5 is transcriptionally regulated by the large-Maf family and mediates IGF-1-induced cell invasion in multiple myeloma : Ark5 as a new molecular determinant of malignant multiple myeloma.2005

    • Author(s)
      Suzuki A, Iida S, et al.
    • Journal Title

      Oncogene 24(46)

      Pages: 6936-6944

    • 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] Reduced-intensity conditioning allogeneic stem transplantation for multiple myeloma : results from the Japan myeloma study group.2005

    • Author(s)
      Shimazaki C, Iida S, et al.
    • Journal Title

      Int J Hematol 81

      Pages: 342-348

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of a novel IKK-b inhibitor on multiple myeloma.2005

    • Author(s)
      Sanda T, Iida S, Ogura H, Asamitsu K, Murata T, Bacon KB, Ueda R, Okamoto T.
    • Journal Title

      Clin Cancer Res 11

      Pages: 1974-1982

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CC Chemokine receptor 4(CCR4) positive diffuse large B-cell lymphoma involving the skin : A case report.2005

    • Author(s)
      Ishida T, Inagaki H, Kusumoto S, Inagaki A, Komatsu H, Iida S, Takeuchi G, Ueda R.
    • Journal Title

      Int J Hematol 81

      Pages: 148-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-myeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis.2005

    • Author(s)
      Sanda T, Kuwano T, Nakao S, Iida S, Ishida T, Komatsu H, Shudo K, Ono M, Ueda R.
    • Journal Title

      Leukemia 19

      Pages: 901-909

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Global real-time quantification/reverse transcription-polymerase chain reaction detecting protooncogenes associated with 14q32 chromosomal translocation in multiple myeloma.2005

    • Author(s)
      Tajima E, Uranishi M, Iida S, Komatsu H, Nitta M, Ueda R.
    • Journal Title

      Haematologica/The Hematol J 90

      Pages: 559-562

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of the API2-MALT1 fusion transcript in cytological specimens of the patients with pulmonary MALT lymphoma.2005

    • Author(s)
      Inagaki H, Li C, Okabe M, Nishikawa M, Niimi T, Iida S, Ueda R.
    • Journal Title

      Int J Hematol 82

      Pages: 59-62

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Multiple myeloma oncogene 1(MUM1)/interferon regulatory factor 4(IRF4) upregulates monokine induced by interferon-gamma(MIG) gene expression in B-cell malignancy.2005

    • Author(s)
      Uranishi M, Iida S, Sanda T, Ishida t, Tajima E, Ito M, Komatsu H, Inagaki H, Ueda R.
    • Journal Title

      Leukemia 19

      Pages: 1471-1478

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ark5 is transcriptionally regulated by the large-Maf family and mediates IGF-1-induced cell invasion in multiple myeloma : Ark5 as a new molecular determinant of malignant multiple myeloma.2005

    • Author(s)
      Suzuki A, Iida S, Kato-Uranishi M, Tajima E, Zhan F, Hanamura I, Huang Y, Ogura T, Takahashi S, Ueda R, Barlogie B, Shaughnessy J, Esumi H.
    • Journal Title

      Oncogene 24(46)

      Pages: 6936-6944

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reduced-intensity conditioning allogeneic stem cell transplantation for multiple myeloma : results from the Japan myeloma study group.2005

    • Author(s)
      Shimazaki C, Fujii H, Yoshida T, Chou T, Nishimura M, Asaoku H, Miyawaki S, Ishii A, Ishida T, Taniwaki M, Iida S, Takagi T, Takatsuki K.
    • Journal Title

      Int J Hematol 81

      Pages: 342-348

    • NAID

      10015652210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anti-tumor effect of a novel IKK-β inhibitor on multiple myeloma.2005

    • Author(s)
      Sanda T, Iida S, et al.
    • Journal Title

      Clin Cancer Res. 11

      Pages: 1974-1982

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Global real-time quantification/reverse transcription-polymerise chain reaction detecting protooncogenes associated with 14g32 chromosomal translocation in multiple myeloma.2005

    • Author(s)
      Tajima E, Iida S, et al.
    • Journal Title

      Haematologica/The Hematol J 90:4

      Pages: 559-562

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Multiple myeloma oncogene 1(MUMI)/interferon regulatory factor 4 (IRF4) upregulates monokine induced by interferon-gamma(MIG) gene expression in B-cell malignancy.2005

    • Author(s)
      Uranishi M, Iida S, et al.
    • Journal Title

      Leukemia 19

      Pages: 1471-1478

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anti-tumor effect of a novel IKK-b inhibitor on multiple myeloma.2005

    • Author(s)
      Sanda T, Ogura H, Iida S, et al.
    • Journal Title

      Clinical Cancer Research (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the recept or for thrombopoietin.4198-4200, 2004.2004

    • Author(s)
      Ding J, Iida S, et al.
    • Journal Title

      Blood 103

      Pages: 4198-4200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CXCR3 and CCR4 Expression in T-cell and NK-cell lymphomas with Special Reference to Clinicopathological Significance for Peripheral T-cell Lymphoma, unspecified.2004

    • Author(s)
      Ishida T, Iida S, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 5494-5500

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene.2004

    • Author(s)
      Kanda-Akano Y, Iida S, et al.
    • Journal Title

      Leuk Lymphoma 45

      Pages: 1559-1567

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The CC chemoine receptor(CCR)4 as a novel molecular target for immunotherapy in adult T-cell leukemia/lymphoma.2004

    • Author(s)
      Ishida T, Iida S, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 7529-7539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.2004

    • Author(s)
      Ding J, Komatsu H, Wakita A, Kato-Uranishi M, Ito M, Satoh A, Tsuboi K, Nitta M, Miyazaki H, Iida S, Ueda R.
    • Journal Title

      Blood 103

      Pages: 4198-4200

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CXCR3 and CCR4 Expression in T-cell and NK-cell lymphomas with Special Reference to Clinicopathological Significance for Peripheral T-cell Lymphoma, unspecified.2004

    • Author(s)
      Ishida T, Inagaki H, Iida S, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 5494-5500

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene.2004

    • Author(s)
      Kanda-Akano Y, Nomura K, Fujita Y, Horiike S, Nishida K, Nagai M, Miura I, Nakamura S, Seto M, Iida S, Ueda R, Taniwaki M.
    • Journal Title

      Leuk Lymphoma 45

      Pages: 1559-1567

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The CC chemoine receptor(CCR)4 as a novel molecular target for immunotherapy in adult T-cell leukemia/lymphoma.2004

    • Author(s)
      Ishida T, Iida S, Akatsuka Y, Ishii T, Miyazaki M, Komatsu H, Inagaki H, Okada N, Fujita T, Shitara K, Akinaga S, Takahashi T, Utsunomiya A, Ueda R.
    • Journal Title

      Clin Cancer Res 10

      Pages: 7529-7539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The CC chemoine receptor(CCR) 4 as a novel molecular target for immunotherapy in adult T-cell leukemia/lymphoma2004

    • Author(s)
      Ishida T, Iida S, Akatsuka Y, et al.
    • Journal Title

      Clinical Cancer Research 10

      Pages: 7529-7539

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene2004

    • Author(s)
      Kanda-Akano Y, Nomura K, Iida S, et al.
    • Journal Title

      Leukemia & Lymphoma 45

      Pages: 1559-1567

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CXCR3 and CCR4 Expression in T-cell and NK-cell lymphomas with Special Reference to Clinicopathological Significance for Peripheral T-cell Lymphoma, unspecified2004

    • Author(s)
      Ishida T., Inagaki H., Iida S., et al.
    • Journal Title

      Clinical Cancer Research 10

      Pages: 5494-5500

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.2004

    • Author(s)
      Ding J, Komatsu H, Iida S, et al.
    • Journal Title

      Blood 103

      Pages: 4198-4200

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Multiple myeloma : From molecular pathogenesis to the development of molecular targeting therapies2004

    • Author(s)
      Iida S.
    • Journal Title

      Educational Program Book(The Joint Meeting of 66^<th>. Annual Japanese Society of Hematology & 46^<th>. Annual Meeting of Japanese Society of Clinical Hematology)

      Pages: 99-107

    • NAID

      10014042901

    • Related Report
      2004 Annual Research Report

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

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