title: Survivin messenger RNA levels in Epstein-Barr virus-positive patients with leukemic low-grade B-cell lymphomas expressing the latent membrane protein 1: evidence of apoptotic function?
abstract: BACKGROUND
  Epstein-Barr virus (EBV) is a ubiquitous pathogen that chronically infects B lymphocytes and is implicated in the pathogenesis of lymphoproliferative diseases. Latent membrane protein 1 (LMP1), the major oncoprotein of the virus, has been shown to inhibit apoptosis and trigger survivin expression in malignant cell lines. LMP1 expression has been detected in patients with chronic lymphocytic leukemia, but its properties have not been studied in patients with low-grade B-cell lymphomas. Recent data show that LMP1 can simultaneously induce and inhibit apoptosis in B cells. We detected LMP1 messenger RNA (mRNA) in patients with leukemic low-grade B-cell lymphoma and correlated the expression of the antiapoptotic molecule survivin to that of LMP1 in this group of patients.
  
  
  METHODS
  Peripheral whole blood from 64 patients with low-grade B-cell lymphoma was tested by quantitative reverse transcriptase-polymerase chain reaction (PCR) for the presence of the BXLF-1 gene of EBV, and positive samples were tested by conventional PCR for LMP1 expression. Accordingly, survivin mRNA levels were measured by quantitative reverse transcriptase PCR in all samples and compared between LMP1-positive (LMP1(+)) and LMP1(-) patients.
  
  
  RESULTS
  The BXLF-1 gene was detected in 27 of 64 patients (42%). LMP1 was expressed in 22 of 27 (81%) EBV(+) patients. Survivin expression was found to be 6.36 times higher in LMP1(-) patients than in LMP1(+) patients (P = .008).
  
  
  CONCLUSIONS
  Our results imply that in patients with non-EBV-related leukemic low-grade B-cell lymphoma, LMP1 expression is possibly correlated to apoptosis, as indicated by the lower survivin mRNA levels in LMP1(+) patients.
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: pandiamantopoulos@gmail.com.
authors.forename: Panagiotis T
authors.initials: PT
authors.lastname: Diamantopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Polonyfi
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sofotasiou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Mantzourani
authors.affiliation: Department of Clinical Hematology, "G. Gennimatas" District General Hospital, Athens, Greece.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Galanopoulos
authors.affiliation: Department of Microbiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Spanakis
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Papadopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Fani
authors.initials: F
authors.lastname: Kalala
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Iliakis
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Danai-Stella
authors.initials: DS
authors.lastname: Zareifi
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Elina
authors.initials: E
authors.lastname: Kodandreopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Angelopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Siakantaris
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Variami
authors.affiliation: Faculty of Biology, School of Physical Sciences, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Panagoula
authors.initials: P
authors.lastname: Kollia
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Vaiopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Pangalis
authors.affiliation: First Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Nora-Athina
authors.initials: NA
authors.lastname: Viniou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000821:virology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D000077022:Survivin; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: C107489:BIRC5 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D014763:Viral Matrix Proteins
keywords: Apoptosis; Chronic B lymphoproliferative disorders; Viral lymphomagenesis