title: Prognostic significance of signal transducer and activator of transcription 5 and 5b expression in Epstein-Barr virus-positive patients with chronic lymphocytic leukemia.
abstract: Signal transducer and activator of transcription (STAT) proteins have been intensively studied in hematologic malignancies, and the efficacy of agents against STATs in lymphomas is already under research. We investigated the expression of total STAT5 and STAT5b in peripheral blood samples of patients with chronic lymphocytic leukemia (CLL) in correlation with the presence of Epstein-Barr Virus (EBV) and its major oncoprotein (latent membrane protein 1, LMP1). The EBV load was measured in the peripheral blood by real-time PCR for the BXLF1 gene and the levels of LMP1 by PCR and ELISA. Western blotting was performed for total STAT5 and STAT5b in protein extracts. STAT5b was only expressed in patients (not in healthy subjects) and STAT5 but particularly STAT5b expression was correlated with the presence of the virus (77.3% vs. 51.2%, P = 0.006 for STAT5b) and to the expression of LMP1 (58.3% vs. 21.6%, P = 0.011 for STAT5b). Moreover, the expression of STAT5b and the presence of EBV and LMP1 were strongly negatively correlated with the overall survival of the patients (log-rank test P = 0.011, 0.015, 0.006, respectively). Double positive (for EBV and STAT5b) patients had the lowest overall survival (log-rank test P = 0.013). This is the first report of a survival disadvantage of EBV+ patients with CLL, and the first time that STAT5b expression is correlated with survival. The correlation of STAT5 expression with the presence of the virus, along with our survival correlations defines a subgroup of patients with CLL that may benefit from anti-STAT agents.
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece. pandiamantopoulos@gmail.com.
authors.forename: Panagiotis T
authors.initials: PT
authors.lastname: Diamantopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sofotasiou
authors.affiliation: Laboratory of Cellular Signaling and Molecular Pharmacology, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
authors.forename: Zafiroula
authors.initials: Z
authors.lastname: Georgoussi
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Nefeli
authors.initials: N
authors.lastname: Giannakopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Papadopoulou
authors.affiliation: Department of Clinical Hematology, G. Gennimatas District General Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Galanopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Elina
authors.initials: E
authors.lastname: Kontandreopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Zervakis
authors.affiliation: Laboratory of Cellular Signaling and Molecular Pharmacology, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
authors.forename: Paschalina
authors.initials: P
authors.lastname: Pallaki
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Fani
authors.initials: F
authors.lastname: Kalala
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kyrtsonis
authors.affiliation: Department of Immunology and Histocompatibility, Laikon General Hospital, Athens, Greece.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Dimitrakopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Angelopoulou
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Spanakis
authors.affiliation: First Department of Internal Medicine, Hematology Unit, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece.
authors.forename: Nora-Athina
authors.initials: NA
authors.lastname: Viniou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D050799:STAT5 Transcription Factor / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D014763:Viral Matrix Proteins
keywords: Chronic lymphocytic leukemia; Epstein-Barr virus; latent membrane protein 1; signal transducer and activator of transcription 5