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

1. eb病毒（EBV）在NK细胞中的感染。从NK细胞疾病病例的研究来看，EBV被认为是侵袭型NK- glpd和NK细胞淋巴瘤的病因。然而，在惰性型NK-GLPD中，EBV似乎与该疾病无关。NK细胞在不同类型NK细胞疾病中的表征。从不同类型NK细胞疾病患者获得的NK细胞，从表面表型、细胞谱系、发育阶段、细胞毒性、t细胞受体（TCR）和IgH基因等方面进行研究。在鼻腔NK细胞淋巴瘤中，恶性NK细胞似乎是被激活的成熟NK细胞，而不是未成熟NK细胞。在NK- glpd中，不确定侵袭型NK- glpd的NK细胞是未成熟细胞还是活化的成熟NK细胞，而发现惰性型NK- glpd的NK细胞是活化的成熟NK细胞。对正常NK细胞、鼻NK淋巴瘤细胞、侵袭型NK- glpd细胞、惰性型NK- glpd细胞和两种NK细胞系的NK细胞进行P-gp表达检测。除1株NK细胞外，其余NK细胞均表达P-gp。此外，环孢素A及其衍生物PSC833的加入抑制了P-gp的功能。由于这些药物对P-gp功能的体外研究，它们的体内功能必须明确。用EBV对NK细胞的体外转化进行了试验。初步研究表明EBV可能感染正常NK细胞和NK细胞系。现在这一发现正被其他技术所证实。

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.