Human T-Cell Leukemia Virus Type I Induces Adult T-Cell Leukemia: From Clinical Aspects to Molecular Mechanisms

Abstract

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.

O vírus linfotrópico de células T humanos tipo 1 (HTLV-1): Quando suspeitar da infecção?

“…There is a prolonged latency period between infection and the appearance of ATL, which is as much as 60 years in Japan and 40 years in Jamaica. 22 Table 3 lists the four major classifications of ATL. 38,39 The leukemic phase of ATL tends to spare the bone marrow; accentuated anemia and thrombocytopenia are not observed.…”

“…In ATL, HTLV expresses the oncogenic capacity of the viral genes, primarily Tax and HBZ, which alter the expression of cellular genes involved in control of cell replication and apoptosis. 16,22 serological and laboratorial diagnosis Initially, lower-cost screening tests such as enzymatic immunoassay or agglutination tests are used. The low specificity of these tests means they often give false-positive results.…”

Human T-Cell Lymphotropic Virus (HTLV-1) and Adult T-Cell Leukemia

“…On the other hand, in the indolent types of ATL, smoldering and chronic types, the abnormality of the nuclear shape is generally milder than that in the acute form of the disease. The second criteria is the presence of antibodies to HTLV-1 in the sera, and the third is the demonstration of monoclonal integration of HTLV-1 provirus in tumor cells by Southern blotting (Yasunaga and Matsuoka 2007).…”

Establishment of cell lines from adult T-cell leukemia cells dependent on negatively charged polymers

“…Its tumorigenesis is related to the accumulation of genomic abnormalities 4,5 ; next-generation sequencing clarified the complicated genomic abnormalities and revealed the activation of the signaling pathway involving nuclear factor κ-B (NFκB) 6 . However, the genomic abnormalities are so divergent that their common pathway still remains to be explored.…”