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Analysis of proviral and cellular genome abnormalities found during disease progression in adult T-cell leukemia/lymphoma

Research Project

Project/Area Number 09671122
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TOMONAGA Masao  Nagasaki University School of Medicine Professor, 医学部, 教授 (40100854)

Co-Investigator(Kenkyū-buntansha) TSUKASAKI Kunihiro  Nagasaki University School of Medicine Assistant, 医学部, 助手 (40274659)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsHTLV-I / ATL / clonal evolution / clonal change / p15 / 16 / RB / progression / multistep carcinogenesis / 成人T細胞白血病・リンパ腫 / 多段階発癌 / 癌抑制遺伝子
Research Abstract

We have investigated on abnormaliteies of human T-lymphotropic virus type-I proviral genomes and cellular genomes in relation to multistep leukemogenesis of adult T-ceII leukemia/lymphoma (ATL) by using cases with ATL which progressed from low grade state of malignancies such as chronic type as well as smouldering type.
1n 13 cases which progressed to overt acute type from the low grade types, consecutive analyses of HTLV-I integration sites disclosed apparent changes in three cases. In two of them, the pattern of TCR beta rearrangement changed also, indicating that a clone distinct from the original low grade clone appeared as acute ATL clone. We desiganted this phenomenon as clonal change. In one case TCR beta rearrangement band was identical to that of the original clone, indicating a clonal evolution.
Consecutive analyses of p15/16 abnormalties revealed that no case showed deletion of them during low grade state, but we found three cases of deletion after progression to acute type. In two of them the HTLV-I integration site was identical to that of the original clone, suggesting clonal evolution by acquisition of the p15/16 deletion. We found no case with Rb abnormality occurring conincidentally with disease progression.
It is interesting to have observed not infrequently the clonal changes in ATL disease progression, which are quite different from the clonal evolution-type disease progression in common maliganancies such as de novo leukemia.. Such a clonal cgange has been reported in Epstein-Barr virus-related B-lymphoid malignancies. In conclusion the clonal change occurring during disease progression may be a specific phenomenon in viral carcinogenesis.

Report

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

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Kunihiro Tsukasaki: "Integration Patterns of HTLV-I Provirus in Relation to the Clinical Course of ATL ; Frequent Clonal Change at Crisis from Indolent Disease" Blood. 89・3. 948-956 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuaki Yamada: "Deletions of p15 and/ or p16 genes as a Poor-Prognosis Factor in Adult T-cell Leukemia" Journal of Clinical Oncology. 15・5. 1778-1785 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kunihiro Tsukasaki: "Integration Patterns of HTLV-I Provirus in Relation to the Clinical Course of ATL ; Frequent Clonal Change at Crisis from Indolent Disease" Blood. 89-3. 948-956 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasuaki Yamada: "Delections of p15 and/or p16 genes as a Poor-Prognosis Factor in Adult T-cell Leukemia" Journal of Clinical Oncology. 15-5. 1778-1785 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kunihiro Tsukasaki: "Integration Patterns of HTLV-I Provirus in Relation to the Clinical Course of ATL;Frequent Clonal Change at Crisis from Indolent Disease" Blood. 89・3. 948-956 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasuaki Yamada: "Deletions of p15 and/or p16 genes as a Poor-Prognosis Factor in Adult T-cell Leukemia" Journal of Clinical Oncology. 15・5. 1778-1785 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kunihiro Tsukasaki: "Integration Patterns of HTLV-I Provirus in Relction to the Clinical Course of ATL : Frequent Clonal Change at Crisis from Indolent Disease" Blood. 89・3. 948-956 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasuaki Yamada: "Deletions of p15 and/or p16 Genes as a Poor-Prognostic Factor in Adult T-cell Leukemia" Journal of Clinical Oncology. 15・5. 1778-1785 (1997)

    • Related Report
      1997 Annual Research Report

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

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