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. Cancer 2010. © 2010 American Cancer Society.

Epstein-Barr virus infection and chronic lymphocytic leukemia: a possible progression factor?

“…More recently, LMP-1 transcriptional activity was detected in a significant proportion of CLL cases (14% vs . 1% of healthy controls) [19]. Notably, CLL patients showing LMP-1 mRNA expression had a higher extent of marrow involvement [19].…”

“…1% of healthy controls) [19]. Notably, CLL patients showing LMP-1 mRNA expression had a higher extent of marrow involvement [19]. Although a confirmation that LMP-1 is expressed also at the protein level is still lacking, available evidence is consistent with a possible role for EBV in the malignant progression of the disease.…”

Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph

“…6,7 Epstein Barr virus control requires a constant lifelong state of alert of the immune system, involving approximately 1% of all T cells, which may decrease with increasing age. 8 A raised EBV-reactivation with age may be reflected in an increased incidence of EBV-driven lymphoproliferative diseases and B-cell lymphomas in the elderly.…”

“…Transcriptional activity of the Epstein Barr virus latent membrane protein 1 (LMP1) with known transforming potential in vitro was recently detected in a significant proportion of chronic lymphocytic leukemia patients. 7 Atypical Epstein Barr virus serological patterns 1,2 appear to be associated with chronic lymphocytic leukemia and its clinical grade independently of age (Online Supplementary Appendix 8). Monoclonal B-CLL are generally EBV negative and the role of Epstein Barr virus, if any, would probably be indirect via B-cell triggering and facilitation of malignant growth.…”

A Human Fab-Based Immunoconjugate Specific for the LMP1 Extracellular Domain Inhibits Nasopharyngeal Carcinoma Growth In Vitro and In Vivo

“…Furthermore, LMP1-positive NPCs are reported to be more progressive than LMP1-negative NPCs and show an increasing tendency of lymph node metastasis (3). Structurally, LMP1 is an integral membrane protein consisting of a short cytoplasmic N-terminus of 20 amino acids, a transmembrane domain with 6 membrane-spanning segments that anchor LMP1 in a patchy distribution along the plasma membrane, and a long cytoplasmic C-terminus of 200 amino acids (4)(5)(6).…”