Epstein-Barr virus latent membrane protein 1 mRNA is expressed in a significant proportion of patients with chronic lymphocytic leukemia

Cancer. 2010 Feb 15;116(4):880-7. doi: 10.1002/cncr.24839.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Bone Marrow / virology
  • Cell Line, Tumor
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / virology*
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • RNA, Viral / metabolism
  • Viral Matrix Proteins / blood
  • Viral Matrix Proteins / metabolism*

Substances

  • EBV-associated membrane antigen, Epstein-Barr virus
  • RNA, Messenger
  • RNA, Viral
  • Viral Matrix Proteins