[Genetic analysis and its clinical implication in adult T-cell leukemia/lymphoma]

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with a dismal prognosis. This disease is caused by human T-cell leukemia virus type-1 (HTLV-1) retrovirus. Not only viral proteins, such as Tax and HBZ, but also additional genetic and epigenetic aberrations, including gain-of-function alterations in the components of T-cell receptor/NF-κB pathway or deteriorating alterations responsible for immune surveillance, are essential for ATL development and progression. Furthermore, recent investigation has demonstrated the effects of genetic and epigenetic alterations prevalently identified in ATL on the disease phenotype and its clinical outcomes. Aggressive ATL is associated with an increased burden of genetic and epigenetic abnormalities. Higher frequencies of TP53 and IRF4 mutations and several copy number alterations, including PD-L1 amplifications and CDKN2A deletions, are more predominant in aggressive than indolent diseases. In contrast, STAT3 mutations are more frequent in indolent ATL. Several genetic alterations, such as PD-L1 amplification, can predict the clinical outcomes independent of established clinical factors. Therefore, ATL subtypes can further be subdivided into genetically distinct subgroups with different prognoses. The genetic profiling of ATL cases has revealed its molecular pathology and should contribute to improved prognostication and management of patients with ATL.