title: Cytokines and Epstein Barr virus (EBV) genes expression in blood chronic lymphocytic leukaemia (CLL) cells and their immortalised CLL cell lines.
abstract: We have encountered two unique chronic lymphocytic leukaemia (CLL) patients, PG and NN. Some blood CLL cells of these patients have been infected and carry Epstein Barr virus (EBV) in vivo. In spite of their early-activated G0/G1 stage of post germinal center (GC) memory cells, ex vivo EBV-carrying blood CLL cells of PG clone expressed LMPs and used specific QUK splice for their EBNA1 expression, similar to the EBV-carrying cells of non-B origin. Interestingly, EBV-carrying CLL cells of NN clone expressed LMP2a and used UK-splice for their EBNA1 expression, similar to the in vivo EBV-carrying high density normal B cells in the blood of healthy individuals. The CLL-derived lines but not normal lymphoblastoid cell line (LCL) used QUK- and YUK-splice for their EBNA1 expression. As expected, LCL and their permanent CLL-derived lines used Cp promoter and up-regulated their EBNA2 expression. Blood CLL cells and the CLL-derived cell lines of these patients spontaneously produced cytokines as shown by microarray assay. The types and quantities of cytokines might relate to their CLL origin and viral strain in the given CLL cells. Neither blood CLL nor their CLL-derived cell lines express any detectable apoptosis-inducer ligands, CD95L or Apo 3L. As a consequence of cell cycle progression, CLL-derived cell lines up-regulated their co-stimulator molecules CD80 and apoptosis-related receptor CD95. Since only the rare EBV-carrying CLL cells grew in vitro, the combination of viral genome and cytokines seems to be critical for the outgrowth of EBV-carrying CLL cells over their EBV-negative counterpart in vitro but not in vivo.
authors.affiliation: Department of Oncology Research Laboratory, Clinical Research Center, Huddinge University Hospital, Stockholm, Sweden. nongnit.laytragoon-lewin@medhs.ki.se
authors.forename: Nongnit
authors.initials: N
authors.lastname: Laytragoon-Lewin
authors.forename: Fu
authors.initials: F
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Castro
authors.forename: Javier
authors.initials: J
authors.lastname: Avila-Carino
authors.forename: Freddi
authors.initials: F
authors.lastname: Lewin
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000821:virology*; D014412:Tumor Virus Infections / Q000097:blood / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1