Preferential selection of human T-cell leukemia virus type I provirus integration sites in leukemic versus carrier states

  • Keitarou Doi
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Xiaolin Wu
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Yuko Taniguchi
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Jun-ichirou Yasunaga
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Yorifumi Satou
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Akihiko Okayama
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Kisato Nosaka
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • Masao Matsuoka
    From the Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD; and the Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

抄録

<jats:title>Abstract</jats:title> <jats:p>Human T-cell leukemia virus type I (HTLV-I) is a causative agent of neoplastic disease, adult T-cell leukemia (ATL). Although the encoding viral proteins play an important role in oncogenesis, the role of the HTLV-I proviral integration site remains unsolved. We determined the integration sites of HTLV-I proviruses in ATL cells and HTLV-I–infected cells in asymptomatic carriers. In carrier and ATL cells, HTLV-I provirus was integrated into the transcriptional unit at frequencies of 26.8% (15/56) and 33.9% (20/59), respectively, which were equivalent to the frequency calculated based on random integration (33.2%). In addition, HTLV-I provirus was prone to integration near the transcriptional start sites in leukemic cells (P = .006), and the transcriptional direction of the provirus was in accordance with that of integrated cellular genes in 70% of cases. More importantly, the integration sites in the carrier cells favored the alphoid repetitive sequences (11/56; 20%) whereas in leukemic cells they disfavored these sequences (2/59; 3.4%). Taken together, during natural course from carrier to onset of ATL, HTLV-I–infected cells with integration sites favorable for viral gene transcription are susceptible to malignant transformation due to increased viral gene expression.</jats:p>

収録刊行物

  • Blood

    Blood 106 (3), 1048-1053, 2005-08-01

    American Society of Hematology

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