Open AccessPrognostic significance of signal transducer and activator of transcription 5 and 5b expression in Epstein–Barr virus‐positive patients with chronic lymphocytic leukemia
Author(s) -
Diamantopoulos Panagiotis T.,
Sofotasiou Maria,
Georgoussi Zafiroula,
Giannakopoulou Nefeli,
Papadopoulou Vasiliki,
Galanopoulos Athanasios,
Kontandreopoulou Elina,
Zervakis Panagiotis,
Pallaki Paschalina,
Kalala Fani,
Kyrtsonis MarieChristine,
Dimitrakopoulou Aglaia,
Vassilakopoulos Theodoros,
Angelopoulou Maria,
Spanakis Nikolaos,
Viniou NoraAthina
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.804
Subject(s) - stat , stat protein , jak stat signaling pathway , stat3 , real time polymerase chain reaction , chronic lymphocytic leukemia , medicine , leukemia , immunology , epstein–barr virus , virus , stat4 , biology , gene , receptor , biochemistry , tyrosine kinase
Abstract Signal transducer and activator of transcription ( STAT ) proteins have been intensively studied in hematologic malignancies, and the efficacy of agents against STAT s in lymphomas is already under research. We investigated the expression of total STAT 5 and STAT 5b 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, LMP 1). The EBV load was measured in the peripheral blood by real‐time PCR for the BXLF 1 gene and the levels of LMP 1 by PCR and ELISA . Western blotting was performed for total STAT 5 and STAT 5b in protein extracts. STAT 5b was only expressed in patients (not in healthy subjects) and STAT 5 but particularly STAT 5b expression was correlated with the presence of the virus (77.3% vs. 51.2%, P = 0.006 for STAT 5b) and to the expression of LMP 1 (58.3% vs. 21.6%, P = 0.011 for STAT 5b). Moreover, the expression of STAT 5b and the presence of EBV and LMP 1 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 STAT 5b) 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 STAT 5b expression is correlated with survival. The correlation of STAT 5 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.