Human T-cell leukemia virus type I induces adult T-cell leukemia: from clinical aspects to molecular mechanisms.
BACKGROUND
Human T-cell leukemia virus type I (HTLV-I) is a causative virus of adult T-cell leukemia (ATL), HTLV-I-associated myelopathy/tropical spastic paraparesis, and HTLV-I-associated uveitis. ATL is a neoplastic disease of CD4-positive T lymphocytes that is characterized by pleomorphic tumor cells with hypersegmented nuclei, termed "flower cells." The mechanisms of leukemogenesis have not been fully clarified.


METHODS
The authors reviewed the virological, clinical, and immunological features of HTLV-I and ATL and summarized recent findings on the oncogenic mechanisms of ATL and therapeutic advances.


RESULTS
Multiple factors, such as viral genes, genetic and epigenetic alterations, and the host immune system, may be implicated in the leukemogenesis of ATL. Among them, viral genes, tax, and HBZ have been thought to play important roles. The prognosis of aggressive-type ATL remains poor, regardless of intensive chemotherapy. Effectiveness of allogeneic stem cell transplantation for ATL has been recently reported.


CONCLUSIONS
Although the precise mechanism of leukemogenesis of ATL remains unclear, recent progress provides important clues in oncogenesis by HTLV-I. Future research should focus on the composition of novel therapeutic strategies, including prevention, based on the evidence in the leukemogenic mechanisms.
Yasunaga
Jun-ichirou
J
Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan. jyasunag@virus.kyoto-u.ac.jp
Matsuoka
Masao
M
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy / Q000821:virology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014764:Viral Proteins / Q000235:genetics
D044966:Anti-Retroviral Agents; D000911:Antibodies, Monoclonal; D016328:NF-kappa B; D014764:Viral Proteins