OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic lymphocyte leukemia (B-CLL) cells for EBV-induced immortalization. STUDY DESIGN/ METHODS: Cells from four B-CLL patients were infected with Epstein-Barr virus (EBV). Noninfected and infected aliquots were exposed to CD40L. Five days later, the cultures were analyzed for cell survival, activation, DNA synthesis, and expression of EBV-encoded and of cellular regulatory proteins retinoblastoma (Rb), p53, recombinant sequence binding protein (RBP)Jk, and PU.1. The proteins were detected by immunoblotting and by immunofluorescence. RESULTS: A proportion of the cells were activated and expressed Epstein-Barr nuclear antigens (EBNAs) and elevated Rb level but not latent membrane protein (LMP)-1 and p53. They did not enter the cell cycle. Exposure to CD40L induced DNA synthesis but it did not modify the expression of the EBNAs. CONCLUSIONS: The virus could activate CLL cells, but the full course of the early events that leads to immortalization--as seen in normal B cells--did not proceed beyond a certain point. Compared to B lymphocytes, the critical point is between activation and initiation of the cell cycle.
OBJECTIVES: To understand the mechanism for the refractoriness of B-chronic lymphocyte leukemia (B-CLL) cells for EBV-induced immortalization. STUDY DESIGN/ METHODS: Cells from four B-CLL patients were infected with Epstein-Barr virus (EBV). Noninfected and infected aliquots were exposed to CD40L. Five days later, the cultures were analyzed for cell survival, activation, DNA synthesis, and expression of EBV-encoded and of cellular regulatory proteins retinoblastoma (Rb), p53, recombinant sequence binding protein (RBP)Jk, and PU.1. The proteins were detected by immunoblotting and by immunofluorescence. RESULTS: A proportion of the cells were activated and expressed Epstein-Barr nuclear antigens (EBNAs) and elevated Rb level but not latent membrane protein (LMP)-1 and p53. They did not enter the cell cycle. Exposure to CD40L induced DNA synthesis but it did not modify the expression of the EBNAs. CONCLUSIONS: The virus could activate CLL cells, but the full course of the early events that leads to immortalization--as seen in normal B cells--did not proceed beyond a certain point. Compared to B lymphocytes, the critical point is between activation and initiation of the cell cycle.
Authors: Kentaro Bandobashi; Anquan Liu; Noémi Nagy; Loránd L Kis; Jun Nishikawa; Magnus Björkholm; George Klein; Eva Klein Journal: Virus Genes Date: 2005-05 Impact factor: 2.332
Authors: Carlo Visco; Erika Falisi; Ken H Young; Michela Pascarella; Omar Perbellini; Giuseppe Carli; Elisabetta Novella; Davide Rossi; Ilaria Giaretta; Chiara Cavallini; Maria Teresa Scupoli; Anita De Rossi; Emanuele Stefano Giovanni D'Amore; Mario Rassu; Gianluca Gaidano; Giovanni Pizzolo; Achille Ambrosetti; Francesco Rodeghiero Journal: Oncotarget Date: 2015-07-30
Authors: Jin-Hua Liang; Rui Gao; Yi Xia; Robert Peter Gale; Rui-Ze Chen; Yu-Qiong Yang; Li Wang; Xiao-Yan Qu; Hai-Rong Qiu; Lei Cao; Min Hong; Rong Wang; Yan Wang; Lei Fan; Yao-Yu Chen; Zhi-Bin Hu; Jian-Yong Li; Wei Xu Journal: Oncotarget Date: 2016-01-12