The purpose of this review is to shed light on the complex oncogenic process of adult T-cell leukemia/lymphoma (ATL). One of the leading causes of ATL is the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is a type C RNA retrovirus that also causes HTLV-1-associated myelopathy (HAM). While the HTLV-1-derived proteins Tax and HBZ have been studied in relation to ATL’s oncogenesis, it is still unclear whether they play a significant role in its development. Tax activates targeted genes and molecules during the early polyclonal stage, while HBZ regulates and inhibits Tax and its actions during the intermediate stage. However, additional oncogenic activities occur in host cells during the monoclonal stage, leading to the development of ATL. The nuclear factor kappa B (NF-kB)/hypoxia inducible factor (HIF)/carbonic anhydrase IX (CA9) axis and the phosphatidylinositol 3-kinase (PI3K)/HIF/CA9 axis are particularly important in ATL oncogenesis. Studies have shown that CA9 inhibitors may provide new therapeutic approaches for treating ATL.
Author(s) Details:
Mitsuru Sakitani,
Institute CCC, Kobe, Hyogo, 651-2242, Japan.
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