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Mutation analysis of c-kit and c-mpl genes in chronic myelogenous leukemia

Research Project

Project/Area Number 09671137
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNippon Medical School

Principal Investigator

INOKUCHI Koiti  Nippon Medical School, Dept.of Internal Medicine, Lecturer, 医学部, 講師 (10203267)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsLEUKEMOGENESIS / c-kit / c-mpl / mutation / CML / bcr / abl / 慢性骨髄性白血病 / C-mpl / C-kit / SCF
Research Abstract

Leukemogenesis was investigated with molecular biological methods. Especially, abnormalities of c-kit and c-mpl genes in chronic myelogenous leukemia (CML) were detected. Some CML patients had abnormal isoform of c-mpl transcript, and others had a point mutation of c-kit genes. Minor type bcr-abl transcript was revealed to make CML patients atypical clinicalcourses other than typical CML.Acute lymphoblastic leukemia with atypical P180 BCR/ABL protein was also atypical clinical course with chemo-resistance. Usually, there are three isoforms of c-mpl transcript In normal control, patients with idiopathic thrombocytopenic purpura and myelodysplastic syndromes (MDS). But, CML patients had abnormal c-mpl transcript without half of exon 11. This abnormality of c-mpl may be clinical heterogeneity of thrombocytosis. Some CML patients had point mutation of codon 541. These CML had remarkable leukocytosis. The same point miutation of codon 541 was occurred in some CML patient at blastic crisis, whose skin has no mutation of codon 541. Biological function of abnormalities of these c-kit and c-mpl proteins are investigating with mutagenesis method.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Inokuchi K 等: "Establishment of a cell line with variant BCR/ABL……" Genes, Chromosomes & Cancer. 23. 227-238 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasukawa M 等: "CD4^+ cyToToxic T-cell cloues specific for bcr-abl 63a2…" Blood. 92. 3355-3361 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K 等: "Heterogenous expression of bcr-abl fusion mRNA in a …" Br.J.Haematology. 97. 837-840 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi H等: "Extramedullery presentation of CML with P190 BCR/ABL" Cancer Genetics Cytogenetics. 102. 74-77 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K 等: "Minimal Residual disease in acute myologenoss leukemia…" Leukemia and Lymphoma. 29. 553-561 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanosaki S 等: "Relationship of microsatellite instability to N-ras…" Cancer. 83. 475-481 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "Establishment of a cell line with variant BCR/ABL breakpoint expressing P180BCR/ABL from late-appearing Philadelphia-positive acute biphenotypic leukemia." Genes, Chromosomes & Cancer. 23. 227-238 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasukawa M,et al.: "CD4+ cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner." Blood. 92. 3355-3361 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "Heterogeneous expression of bcr-abl fusion mRNA in a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia." British Journal of Haematology. 97. 837-840 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi H: "Extramedullary presentation of chronic myelogenous leukemia with P190 BCR/ABL transcripts." Cancer Genetics Cytogenetics. 102. 74-77 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Futaki M,et al.: "Possible transforming activity of Interferon regulatory factor 2 in tumorigenicity assay of NIH3T3 cells transfected with DNA from chronic myelogenous leukemia.Patients." Leukemia Research. 20. 601-605 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "DCC protein expression in Hematopoietic cell populations and its relation to leukemogenesis." Journal of Clinical Investigation. 97. 1-6 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "Minimal residual disease of the patients with acute myelogenous leukemia having PML/RAR or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow." Leukemia and Lymphoma. 29. 553-561 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanosaki S,et al.: "Relationship of microsatellite instability to N-ras mutation and duration of disease-free survival in acute leukemia." Cancer. 83. 475-481 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hamaguchi H,et al.: "Alteration in the DCC gene and DCC protein in a novel human myeloid leukemia cell line with trisomy 18 established from overt leukemia after myelodysplastic syndrome." International Journal of Hematology. 67. 153-164 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hanawa H,et al.: "Dual rearrangement of immunoglobulin and T-cell receptor genes in a case of splenic lymphoma with villous lymphocytes." Leukemia and Lymphoma. 18. 357-360 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "Establishment and characterization of villous lymphoma cell line from splenic B-cell lymphoma." Leukemia Research. 19. 817-822 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Inokuchi K,et al.: "Loss of expression of the human MSH3 gene in hematological malignancies." Biochemical and Biophysical Research Communications. 214. 171-179 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikezoe T,et al.: "Inactivation of the DCC tumor suppressorgene in a B-cell lymphoma cell line with the alteration of Chromosome 18." American Journal of Hematology. 50. 124-132 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sueoka N,et al.: "Genotype configuration in a case of primary gastric lymphoma with T-cell phenotype." Cancer Genetics Cytogenetics. 101. 103-108 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamaguchi H,et al.: "Establishment of a near-triploid human B-cell lymphoma cell line with t (14 ; 18) and a p53 gene point mutation." British Journal of Haematology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Koiti Inokuchi 等: "Establishment of a cell line with variant BCR/ABL…" Genes Chromosomes & Cancer. 23. 227-238 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masaki Yasukawa 等: "CD4^+ Cytotoxic T-cell cloues specific for bcr-abl b3a2…" Blood. 92,9. 3355-3361 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakae Tanosaki: "Relation between microsatellite instability and N-ras" Cancer. 83. 475-481 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inokuchi K.,et al.: "Pure red cell aplasia overted at an interval of 12 years…" American J.Hematology. 53巻. 141- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inokuchi k.,et al: "Heterogenous expression of ber-ab'l fusion in RiA in a…" British J Haematology. 97巻. 837-840 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tajika K.,et al.: "IL-6 and SCF exet different effects on megalcaryoyte…" British J Haewatology. 100巻. 105-111 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sveoka N.,et al: "Geuotype configuration in a case of Prima ry Gastric…" Caucer Genetics Cytogeuetics. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yawaguchi H.,et al: "Extramedullasy preceutection of CML with P190 BCR/ABL…" Cancer Geuetics Cytogonetics. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Inokvchi K.,et al: "Establishment of a cell line with varicnl BCR/ABL…" Genes Chrowosomes&Cancer. (in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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