Multistep Oncogenesis of Adult T-cell Leukemia/ Lymphoma and Significance of Carbon Anhydrase IX Activated via NF-\(_K\)B and PI3K

Abstract

The objective of this review is to explain the multistep oncogenesis of adult T-cell leukemia/lymphoma (ATL). Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult ATL. Both ATL and HTLV-1-associated myelopathy (HAM) are caused by the type C RNA retrovirus known as the HTLV-1. It has remained a mystery as to why the HTLV-1-derived proteins may not have played significant roles in the conclusion of ATL's oncogenesis. Oncogenic processes of ATL are highly complicated, and there is an enigma that the HTLV-1-derived proteins Tax and HBZ may not play major roles in completion of its oncogenesis. Tax activates several targeted genes and molecules during the early polyclonal stage, but HBZ regulates and inhibits Tax and its actions during the intermediate stage. Additional oncogenic activities in host cells complete the oncogenesis of ATL at the monoclonal stage. In particular, the nuclear factor kappa B (NF-\(_K\)B)/hypoxia inducible factor (HIF)/carbon anhydrase IX (CA9) axis and the phosphatidylinositol 3-kinase (PI3K)/HIF/CA9 axis play essential roles in ATL oncogenesis. The in vitro experimental studies with CA9 inhibitors also present new therapeutic approaches for treating ATL.