BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with Richter transformation in patients with chronic lymphocytic leukemia (CLL). METHODS: A direct isothermal mRNA amplification method was developed for detection of EBV latent membrane protein 1 (LMP1) mRNA transcriptional activity in the peripheral blood of 135 chronic lymphocytic leukemia patients and 98 hematologically healthy control subjects. RESULTS: EBV LMP1 mRNA transcripts were found in 19 of 135 (14%) of the CLL cases, but only 1% of the healthy controls (P < .0001). In contrast, 23 solid tumor patients tested negative for EBV LMP1 transcripts. In a later cohort of patients after hematopoietic stem cell transplantation, 4 of 7 patients with Hodgkin lymphoma or Burkitt lymphoma had EBV LMP1 detected. In a preliminary analysis, outcome data were available for 88 of the 135 patients with CLL. EBV LMP1 mRNA positivity was associated with a significantly increased degree of histologically demonstrated bone marrow involvement by CLL (P = .003, Mann-Whitney U test). CONCLUSIONS: EBV LMP1 mRNA transcriptional activity was observed in a significant proportion of CLL patients. Transcription of the EBV LMP1, a late gene with known transforming potential in vitro, suggests that EBV activation plays a role in CLL disease progression. Thus, EBV LMP1 expression in CLL patients may be a factor involved in the genesis of refractory disease.
BACKGROUND:Epstein-Barr virus (EBV) infection has been associated with Richter transformation in patients with chronic lymphocytic leukemia (CLL). METHODS: A direct isothermal mRNA amplification method was developed for detection of EBV latent membrane protein 1 (LMP1) mRNA transcriptional activity in the peripheral blood of 135 chronic lymphocytic leukemiapatients and 98 hematologically healthy control subjects. RESULTS:EBV LMP1 mRNA transcripts were found in 19 of 135 (14%) of the CLL cases, but only 1% of the healthy controls (P < .0001). In contrast, 23 solid tumorpatients tested negative for EBV LMP1 transcripts. In a later cohort of patients after hematopoietic stem cell transplantation, 4 of 7 patients with Hodgkin lymphoma or Burkitt lymphoma had EBV LMP1 detected. In a preliminary analysis, outcome data were available for 88 of the 135 patients with CLL. EBV LMP1 mRNA positivity was associated with a significantly increased degree of histologically demonstrated bone marrow involvement by CLL (P = .003, Mann-Whitney U test). CONCLUSIONS:EBV LMP1 mRNA transcriptional activity was observed in a significant proportion of CLL patients. Transcription of the EBV LMP1, a late gene with known transforming potential in vitro, suggests that EBV activation plays a role in CLL disease progression. Thus, EBV LMP1 expression in CLL patients may be a factor involved in the genesis of refractory disease.
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Authors: Alessandra Ferrajoli; Cristina Ivan; Maria Ciccone; Masayoshi Shimizu; Yoshiaki Kita; Masahisha Ohtsuka; Lucilla D'Abundo; Jun Qiang; Susan Lerner; Nazila Nouraee; Kari G Rabe; Laura Z Rassenti; Katrien Van Roosbroeck; John T Manning; Yuan Yuan; Xinna Zhang; Tait D Shanafelt; William G Wierda; Silvia Sabbioni; Jeffrey J Tarrand; Zeev Estrov; Milan Radovich; Han Liang; Massimo Negrini; Thomas J Kipps; Neil E Kay; Michael Keating; George A Calin Journal: EBioMedicine Date: 2015-04-29 Impact factor: 8.143
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