Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth

Abstract

// Marco Pizzi 1,* , Francesco Piazza 2,3* , Claudio Agostinelli 4 , Fabio Fuligni 4 , Pietro Benvenuti 1 , Elisa Mandato 2,3 , Alessandro Casellato 2,3 , Massimo Rugge 1 , Gianpietro Semenzato 2,3 and Stefano A. Pileri 4 1 Department of Medicine, Surgical Pathology and Cytopathology Unit, DIMED University of Padua, Padua, Italy 2 Department of Medicine, Hematology and Clinical Immunology Branch, DIMED University of Padua, Padua, Italy 3 Venetian Institute of Molecular Medicine (VIMM), Padua, Italy 4 Department of Experimental, Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy * These authors have contributed equally to this work Correspondence to: Francesco Piazza, email: // Keywords : CK2, Non-Hodgkin Lymphoma, CX-4945, B-cell Received : January 11, 2015 Accepted : January 28, 2015 Published : January 31, 2015 Abstract Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of α catalytic and β regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2α immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-κB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL.