Common cytological and cytogenetic features of Epstein‐Barr virus (EBV)‐positive natural killer (NK) cells and cell lines derived from patients with nasal T/NK‐cell lymphomas, chronic active EBV infection and hydroa vacciniforme‐like eruptions

Abstract

Summary. In this study, we describe the cytological and cytogenetic features of six Epstein-Barr virus (EBV)-infected natural killer (NK) cell clones. Three cell clones, SNK-1, -3 and -6, were derived from patients with nasal T/NK-cell lymphomas; two cell clones, SNK-5 and -10, were isolated from patients with chronic active EBV infection (CAEBV); and the other cell clone, SNK-11, was from a patient with hydroa vacciniforme (HV)-like eruptions. An analysis of the number of EBV-terminal repeats showed that the SNK cell clones had monoclonal EBV genomes identical to the original EBV-infected cells of the respective patients, and SNK cells had the type II latency of EBV infection, suggesting that not only the cell clones isolated from nasal T/NK-cell lymphomas but also those isolated from CAEBV and HV-like eruptions had been transformed by EBV to a certain degree. Cytogenetic analysis detected deletions in chromosome 6q in five out of the six SNK cell clones, while 6q was not deleted in four control cell lines of T-cell lineage. This suggested that a 6q deletion is a characteristic feature of EBV-positive NK cells, which proliferated in the diseased individuals. The results showed that EBV-positive NK cells in malignant and non-malignant lymphoproliferative diseases shared common cytological and cytogenetic features.

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

“…18 The geneset-enrichment-analysis findings of chromosome 6q gene enrichment in gd-PTCL (NHS) compared with NKCL is likely related to the frequent deletion of 6q in the NK-cell counterpart. 31 This deletion is not observed in the gd T-cell lines, 41 and may be similarly true for gd-PTCLs (NHS) as well. Gene signatures associated with IL12 signaling, shown to be critical for gd T-cell proliferation by resisting apoptosis, 42 were up-regulated in gd-PTCL (NHS) compared with NKCL.…”

Epstein‐Barr virus (EBV) latent membrane protein‐1‐specific cytotoxic T lymphocytes targeting EBV‐carrying natural killer cell malignancies

“…4B. H7 specifically lysed exogenous DLMP1-expressing, but not EGFP-expressing LCL in the 4-h CTL assay Cytotoxic activities of the LMP1-specific CTL clone against EBV-infected NK cell lines EBV LMP1 is expressed in LCL with other proteins as latency III and also in NK/T cell malignancies as latency II [7]. In a final set of experiments, we tested the lytic activity of H7 against EBV-carrying NK cell lines as representative of EBV latency II malignancies and retaining characteristics of the original tumors, such as identical EBV clonality [6,7,33].…”

“…EBVtransformed B-LCL were established as described previously [48] and cultured in RPMI 1640 medium (Sigma Chemical Co., St. Louis, MO) supplemented with 10% fetal calf serum (PAA Laboratories, Pasching, Austria), 2 mM L-glutamine, 50 U/mL penicillin, 50 lg/mL streptomycin, and 50 lg/mL kanamycin. EBV-carrying NK cell lines SNK-6 [6] and SNK-10 [7] were kindly provided by Dr. Shimizu (Tokyo Medical and Dental University, Tokyo, Japan). Another EBV-carrying NK cell line, HANK-1 [33], was generously donated by Dr. Kagami (Aichi Cancer Center Hospital).…”

“…Chronic active EBV infection (CAEBV) is another disorder whereby EBV infects mainly NK/T cells to cause life-threatening lymphoproliferative disease [5]. EBV-infected NK cells express LMP1 [5][6][7], a transmembrane oncoprotein that enhances cell survival through up-regulation of anti-apoptotic genes [2]. Expression of LMP1 is essential for growth transformation of human B lymphocytes and is necessary for the proliferation of human monocytes under EBV-infected conditions [2].…”

“…Gottschalk et al [20] reported effective induction of polyclonal LMP1-specific CTL using DC infected with a recombinant adenovirus expressing an N-terminally truncated, nontoxic LMP1 mutant. EBVpositive NK/T cell malignancies express EBNA1 and LMP1 as potential CTL targets [6,7], but it has not been demonstrated that such NK/T cells can process LMP1 and generate HLA-restricted epitopes, so that they are susceptible to CTL-mediated cytolysis.…”