title: Epstein-Barr virus latent membrane protein 1 mRNA is expressed in a significant proportion of patients with chronic lymphocytic leukemia.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jtarrand@mdanderson.org
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Tarrand
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Rocco P
authors.initials: RP
authors.lastname: LaSala
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Han
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000097:blood / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins