Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

Nature killer (NK)/T cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare tumors with higher prevalence in Asia, Central and South America, which are etiologically related to the Epstein Barr virus (EBV). Proteins encoded by EBV genes and non-coding viral RNAs expressed on the infected cells are involved in immune deregulation and cell transformation and lymphomagenesis occur as a consequence of multiple oncogenic events. Complex chromosomal abnormalities are frequent and loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. In accordance, many genes are differentially expressed, often due to gene deletion, mutation or methylation. These include, among others, tumor suppressor genes and oncogenes, as wells as genes involved in cell signal transducer pathways, cell survival and apoptosis, cell cycle, cell motility and cell adhesion, as well as in cell communication through cytokine networks. Consequently many biochemical pathways are affected in NK-cell neoplasms, which could contribute to cancer development and progression, as well as to disease manifestations. This review focuses on the molecular and biochemical mechanisms by which EBV induces NK-cell lymphomagenesis, disrupting genes and molecules involved in crucial biological processes. Improving the knowledge in this subject will help to better understand the disease biology and clinical manifestations and to develop new treatment approaches for the NK-cell malignancies