Essential Role of Carbon Anhydrase IX, Activated Via the Nuclear Factor-κB and Phosphatidylinositol 3-Kinase Signaling Pathways, In Multistep Oncogenesis of Adult T-Cell Leukemia/Lymphoma Caused by Human T-Cell Leukemia Virus Type 1

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia/lymphoma (ATL). 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. Thus several models of multistep oncogenesis have been proposed. In this review, first, the multistep oncogenesis models of ATL were concisely presented. Then, additional oncogenic events in host cells, probably independent of Tax and HBZ, were summarized. In particular, importance of the nuclear factor kappa B (NFκB)/hypoxia inducible factor (HIF)/carbon anhydrase IX (CA9) axis and the phosphatidylinositol 3-kinase (PI3K)/HIF/CA9 axis at the final stage of its oncogenesis was discussed.