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2001 Fiscal Year Final Research Report Summary

HTLV-I associated lymph node and HTLV-I pathogenesis.

Research Project

Project/Area Number 11470051
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionFukuoka University

Principal Investigator

OHSHIMA Koichi  School of Medicine, Professor, 医学部, 助教授 (50203766)

Co-Investigator(Kenkyū-buntansha) HARAOKA Seiji  Fukuoka Univ. Chikushi Hospital, Assistant, 筑紫病院, 助手 (40251053)
KIKUCHI Masahiro  School of Medicine, Professor, 医学部, 教授 (80078774)
Project Period (FY) 1999 – 2001
KeywordsATLL / HTLV-I / provirus / FISH / I-PCR / DcR3 / BUBI / mutation
Research Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type I (HTLVI), and the histology usually indicates a pleomorphic type, but the histology is not uniform. To clarify the relation between the histological classification and prognosis, we reclassified 572 cases with nodal T-cell lymphoma. In all cases, the clonal integration of HTLV-I proviral DNA was examined, using a Southern blot analysis. 572 cases were classified into 3 groups ; (A) the cases with clonal integration [247 cases], (B) cases with AThA, and those without clonal integration of HTLV-I proviral DNA [66 cases}, (C) cases without A ILA [259 cases]. Group A clinically showed a poorer prognosis than groups B and C. In conclusion, group Awas determined to be ATLL (HTLV-I associated T-cell lymphoma). (Br J haematol 1998, 101, 703-11)
ATLL demonstrate clonal chromosome abnormalities, but the karyotypes are very complicated in both number and structure. There are no specific ka … More ryotype abnormalities in ATLL. We investigated the integration site of HTLY-I, using inverse-PCR and FISH. The random integration was confirmed. In 15 of the 18 cases, the chromosomes with HTLV-I integration showed abnormalities, and, especially in 2 cases with simple chromosome abnonnalities, HILV-I integrated int the abnormal chromosome, but not into the normal chromosome. The HTLY-I proviral integration thus seems to, be associated with chromosome abnormalities. (Cancer Letters 1998, 132, 203-12)
The recently identified decoy receptor 3 (DcR3) binds to Fa.sL and inhibits FasL-induced apoptosis, and is considered to play a role in the immune escape system of neoplastic cells. We analysed the amplification and expression of DcR3, using dot blot and in situ hybridization (ISH), in 45 cases, which included 17 cases with Epstein-Barr virus (EBV) associated lymphorna, 7 cases with adult T-cell leukemia lymphoma (AILL). EBV-associated PAL and NKL exhibited DcR3 amplification and expression in lymphoma cells. AILL also showed DcR3 expression and amplification. The DcR3 expression was not in the reactive cells. (Cancer Letter, 2000, 160, 89-97)
The BUB gene is a component of the mitotic checkpoint in budding yeast. Recently, human homologues of the BUB were identified and mutant alleles of hBUB1 and hBUBR1 were detected in two colorectal tumor cell lines. We examined the role of checkpoint gene in the chromosomal abnormalities of ATLL by investigating mutations of hBUB1 and hBUBR1, and MIN of replication errors of BAX, insulin-like growth factor, and transforming growth factor type II. Significant mutations/deletion of hBUB1 or hBUBR1 were detected in 4 of 10 cases with ATLL. In contrast, only one of eight B cell lymphomas showed nonsense mutation of hBUBR1.None of the ATLL and B cell lymphomas showed MIN. (Cancer Letters, 2000, 158, 141-50) Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ohshima K, Shimazaki K.Sugihara M. et al.: "Clinicopathological findings of virus-associated hemophagocytic syndrome in bone marrow : association with Epstein-Barr virus and apoptosis"Pathol.Int.. 49. 533-540 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Suzumiya J, Sato M, et al.: "Survival of patients with HTLV-I-associated lymph node lesions"J.Pathol.. 189. 539-545 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Haraoka S, Yoshioka S. et al.: "Mutation analysis of mitotic checkpoint genes (hBUB and hBUBR1) and microsatellite instability in adult T-cell leukemia/lymphoma"Cancer Letter. 158. 141-150 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Haraoka S, Sugihara M, et al.: "Amplification and expression of a decoy receptor for Fas ligand (DcR3) in virus 'EBV or HTLV-I) associated lymphomas"Cancer Letter. 160. 89-97 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Muta K, Nakashima M, et al.: "Expression of human tumor-associated antigen RCAS1 in Reed-Steinberg cells in association with Epstein-Barr virus infection : a potential mechanism of immune evasion"Int.J.Cancer. 93. 91-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Muta H, Wakasaki C, et al.: "Bcl10 expression, rearrangement and mutation in MALT lymphoma : correlation with expression of nuclear factor-kappa B"Int.J.Oncol.. 19. 283-289 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohshima K, Shimazaki K, Sugihara, M, Suzumiya J Kanda M, Kawasaki C, Kikuchi M: "Clinieopatho-logical findings of virus-associated hemophago-cytic syndrome in bone marrow : association withEpstein-Barr virus and apoptosis."Patol. Int.. 49. 533-540 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima K, Suzumiya J, Sato M, Kanda M, -Shimazaki K, Kawasaki C, Haraoka S, Kikuchi M:: "Survival of patients with HTLV-I-associated 'lymph node lesions."J. Pathol.. 189. 539-545 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima K, Haraoka S, Yoshioka S, Hamasaki M, Fujiki T, Suzumiya J, Kawasaki C, Kanda M, Kikuchi.M: "Mutation analysis of mitotic check-point genes (hBUB and hBUBRI) and microsatel-lite instability in adult T-cell leukemia/lymphoma."Cancer Letter. 158. 141-150 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima K, Haraoka S, Sugihara M, Suzumiya J, Kawasaki C, Kanda M, Kikuchi M: "Amplificationand expression of a decoy receptor for Fas ligand (DcR3) in virus (EBV or HTLV-I) associated lymphomas."Cancer Letter. 160. 89-97 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima K, Muta K, Nakashima M, Haraoka S, Tutiya T, Suzumiya J, Kawasaki C, Watanabe T, Kikuchi M: "Expression of human tumor-associatedantigen EfcASl in Reed-Sternberg cells in association with Epstein-Barr virus infection : a potential mechanism of immune evasion."Int. J. Cancer. 93. 91-96 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohshima K, Muta H, Kawasaki C, Muta K, Deyev V, Kanda M, Kumano Y, Podack E, Kikuchi M:: "Bc110.expression, rearrangement and mutation in MALTlymphoma : correlation with expression ofnuclear factor-kappa B."Int. J. Oncol.. 19. 283-289 (2001)

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

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Published: 2003-09-17  

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