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2004 Fiscal Year Final Research Report Summary

Active mutation of c-kit gene in acute myeloid leukemia

Research Project

Project/Area Number 15591002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionMie University

Principal Investigator

NISHII Kazuhiro  Mie University, Faculty of Medicine, Research Associate, 医学部, 助手 (50332713)

Project Period (FY) 2003 – 2004
Keywordsc-kit / mutation / acute myeloid leukemia / t(8;21) / prognostic factor / tyrosine kinase / abnormal chromosome
Research Abstract

The (8;21) translocation is one of the most common chromosomal abnormality in AML and is associated with good clinical outcome. However, the clinical features of t(8;21)AML with additional genetic aberrations such as mutation have not been well elucidated. In this study, we examined for the KIT mutation in 77 adult patients with de novo AML (M2 subtype) : 43 cases with t(8;21) and 34 cases without t(8;21). The juxtamembrane domain of KIT did not exhibit mutation, while mutation in the intracellular tyrosine kinase domain was detected at Asp816 in 7 of 77 cases and all these seven cases had t(8;21)(16.3% in t(8;21)AML). Western blotting revealed stem cell factor(SCF)-independent KIT activation in AML cells with mutations. Among t(8;21)AML, patients with mutations were significantly associated with leukocytosis (P=0.002) and poor overall survival (P<0.0001;5 year survival, 0% vs 73%). These cells with mutations highly expressed CD18 (P=0.01) and CD56 (P=0.005). When the Asp816 mutation was transfected into a SCF-dependent cell line, Mo7e, the cells grew rapidly and exhibited SCF-independent proliferation. These results indicate that Asp816 mutations of KIT are potentially suitable prognostic genetic markers for the t(8;21)AML patients and t(8;21)AML with mutations in KIT may be a distinctive subtype of t(8;21)AML.

  • Research Products

    (19 results)

All 2005 2004 2003

All Journal Article (19 results)

  • [Journal Article] IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.2005

    • Author(s)
      Miyashita H, Katayama N, Fujieda A, at al.
    • Journal Title

      Int J Oncol 26

      Pages: 731-735

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.2005

    • Author(s)
      Miyashita H, Katayama N, Fujieda A, et al.
    • Journal Title

      Int J Oncol 26

      Pages: 731-735

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Up-regulated production of IL-6, but not IL-10, by Interferon-a induces SOCS3 expression and attenuates STAT1 phosphorylation in myeloma cells.2004

    • Author(s)
      Usui E, Nishii K, Katayama N, et al.
    • Journal Title

      Hematology J 5

      Pages: 505-512

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fluorescent in situ hybridization analysis of Philadelphia chromosome-negative chronic myeloid leukemia with bcrlabl fusion gene.2004

    • Author(s)
      Monma F, Nishi K, Yamamori S, et al.
    • Journal Title

      Int J Hematol 80

      Pages: 155-158

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Acute myeloid leukemia with t(8;21)(q22;q22) manifesting as granulocytic sarcomas in the rhinopharynx at relapse after high-dose cytarabine consolidation : case report and review of the literature.2004

    • Author(s)
      Sugimoto Y, Nishii K, Sakakura M, et al.
    • Journal Title

      Hematology J 5

      Pages: 84-89

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Up-regulated production of IL-6, but not IL-10, by Interferon-□□□induces SOCS3 expression and attenuates STAT1 phosphorylation in myeloma cells.2004

    • Author(s)
      Usui E, Nishii K, Katayama N, et al.
    • Journal Title

      Hematology J 5

      Pages: 505-512

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Fluorescent in situ hybridization analysis of Philadelphia chromosome-negative chronic myeloid leukemia with bcr/abl fusion gene.2004

    • Author(s)
      Monma F, Nishi K, Yamamori S, et al.
    • Journal Title

      Int J Hematol 80

      Pages: 155-158

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Case of chronic-phase chronic myelogenous leukemia with an abdominal hematopoietic tumor of leukemic clone origin.2004

    • Author(s)
      Sakakura M, OhishiK, Nomura K, Katayama N, Nishii K, et al.
    • Journal Title

      Am J Hematol 77

      Pages: 157-170

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reprogramming of human post-mitotic neutrophils into macrophages by growth factors.2004

    • Author(s)
      Araki H, Katayama N, Yamashita Y, Mano H, Fujieda A, Usui E, Mitani H, Ohishi K, Nishii K, et al.
    • Journal Title

      Blood 103

      Pages: 2973-2980

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CD21S antigen expression in tumor cells of diffuse large B-cell lymphomas is an independent prognostic factor indicating better overall survival.2004

    • Author(s)
      Ogawa S, Yamaguchi M, Oka K, Taniguchi M, Ito M, Nishii K, et al.
    • Journal Title

      Br J Haematol 125

      Pages: 180-186

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hemostatic abnormalities and changes following bone marrow transplantation.2004

    • Author(s)
      Matsumoto T, Wada H, Nishiyama H, Hirano T, Sakakura M, Nishii K, et al.
    • Journal Title

      Clin Appl Thromb Hemost 10

      Pages: 341-350

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Activities of granulocyte-macrophage colony-stimulating factor and interleukein-3 on monocytes2004

    • Author(s)
      Suzuki H, Katayama N, Ikuta Y, Mukai K, Fujita A, Mitani H, Araki H, Miyashita H, Hoshino N, Nishikawa H, Nishii K, et al.
    • Journal Title

      Am J Hematol 75

      Pages: 179-189

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] AML with t(8;21) and trisomy 4 : possible involvement of c-kit? / Reply to SE Langabeer et al.2003

    • Author(s)
      Lorenzo F V, Nishii K. Usui E, et al.
    • Journal Title

      Leukemia 17

      Pages: 1915-1916

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality : Concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML.2003

    • Author(s)
      Nishii K, Usui E, Katayama N, et al.
    • Journal Title

      Leukemia 17

      Pages: 731-737

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] AML with t(8;21) and trisomy 4 : possible involvement of c-kit?2003

    • Author(s)
      Lorenzo FV, Nishii K, Usui E, et al.
    • Journal Title

      Leukemia(Reply to SE Langabeer et al.) 17

      Pages: 1915-1916

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characteristics of t(8;21) acute myeloid leukemia(AML) with additional chromosomal abnormality : Concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML.2003

    • Author(s)
      Nishii K, Usui E, Katayama N, et al.
    • Journal Title

      Leukemia 17

      Pages: 731-737

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia for the M0 subtype.2003

    • Author(s)
      Matsuno N, Osato M, Yamashita N, Yanagida M, Nanri T, Fukushima T, Motoji T, Kusumoto S, Towatari M, Suzuki R, Naoe T, Nishii K, et al.
    • Journal Title

      Leukemia 17

      Pages: 2492-2499

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17)(q22;q12)(PML/RARA□).2003

    • Author(s)
      Morikawa J, Li H, Kim S, Nishii K, et al.
    • Journal Title

      Int J Oncol 23

      Pages: 617-625

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T-cell and natural killer (NK)/T-cell malignancies.2003

    • Author(s)
      Nakatsuka S-I, Takakuwa T, Tomita Y, Hoshida Y, Nishiu M, Yamaguchi M, Nishii K, Yang W-I, Aozasa K
    • Journal Title

      Cancer Sci 94

      Pages: 87-91

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

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Published: 2006-07-11  

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