Epstein-Barr virus-infected natural killer cell leukemia

Natural killer cell leukemia (NK leukemia) is an aggressive form of lymphop roliferative disease of granular lymphocytes, and frequently complicates fu lminant hemophagocytic lymphohistiocytosis. NK leukemia cells usually posse ss a single episomal form of Epstein-Barr virus (EBV), and therefore origin ate from a single EBV-infected NK cell. The NK leukemia cells lack endogeno us Bcl-2 expression and are sensitive to apoptotic cell death. However, the y constitutively produce interferon-gamma and maintain their survival in an autocrine fashion. The interferon-gamma released from NK leukemia cells ma y trigger the occurrence of hemophagocytic lymphohistiocytosis through acti vating macrophages/histiocytes. In the primary infection of EBV, T cells in fected with the episomal form of EBV sometimes produce a high amount of int erferon-gamma that may lead to the occurrence of hemophagocytic lymphohisti ocytosis. Thus, it is important to determine the role of EBV in the increas ed production of interferon-gamma that occurs in EBV-infected T and NK cell s to clarify the developmental mechanism of NK leukemia and its paraneoplas tic hemophagocytic lymphohistiocytosis.