Etiology, pathopysiology and treatment of NK cell-lineage leukemias and lymphomas

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1. Infection of Epstein-Barr virus (EBV) in NK cells.From the studies of cases of NK cell disorders, EBV was considered to be the etiologic agentin aggressive-type NK-GLPD and NK-cell lymphomas. In indolent-type NK-GLPD,however, EBV seemed to be unrelated to the disorder.2. Characterization of NK cells in various types of NK-cell disorders.NK cells obtained from patients with various types of NK-cell disorders were studied in terms of surface phenotype, cell lineage, developmental stage, cytotoxicity, and T-cell receptor (TCR) and IgH genes. In nasal NK-cell lymphoma, malignant NK cells seemed to be activated mature NK cells, but not to be immature NK cells. In NK-GLPD,it is uncertain whether NK cells of aggressive-type NK-GLPD are immature cell sor activated mature NK cells, and NK cells of indolent-type NK-GLPD were found to be activated mature NK cells.3. Expression of multidrug resistance (MDR) 1-coded P-glycoprotein (P-gp) on NK cellsNK cells including normal NK cells, nasal NK lymphoma cells, aggressive type NK-GLPD cells, indolent-type NK-GLPD cells, and two NK-cell lines were tested fortheir expression of P-gp. Except one NK-cell line, all the NK cells tested were found to express P-gp. Further, the function of P-gp was inhibited by the addition of cyclosporin A and its derivative PSC833. Because of these in vitro study of these drugs on P-gp function, their in vivo function must be delineated.4. Transformation of NK cells with EBVIn vitro transformation of NK cells with EBV has been tried. A preliminary study indicates the possible infection of EBV into normal NK cells and a NK cell line. Now the finding is being confirmed by other techniques.