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

Authors


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. Cancer 2010. © 2010 American Cancer Society.

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