Epstein-Barr virus-infected natural killer cell leukemia

Natural killer cell leukemia (NK leukemia) is an aggressive form of lymphoproliferative disease of granular lymphocytes, and frequently complicates fulminant hemophagocytic lymphohistiocytosis. NK leukemia cells usually possess a single episomal form of Epstein-Barr virus (EBV), and therefore originate from a single EBV-infected NK cell. The NK leukemia cells lack endogenous Bcl-2 expression and are sensitive to apoptotic cell death. However, they constitutively produce interferon-γ and main their survival in an autocrine fashion. The interferon-γ released from NK leukemia cells may trigger the occurrence of hemophagocytic lymphohistiocytosis through activating macrophages/histiocytes. In the primary infection of EBV, T cells infected with the episomal form of EBV sometimes produce a high amount of interferon-γ that may lead to the occurrence of hemophagocytic lymphohistiocytosis. Thus, it is important to determine the role of EBV in the increased production of interferon-γ that occurs in EBV-infected T and NK cells to clarify the developmental mechanism of NK leukemia and its paraneoplastic hemophagocytic lymphohistiocytosis.