title: Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.
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.
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, DIMED University of Padua, Padua, Italy.
authors: Marco
authors: M
authors: Pizzi
authors: Department of Medicine, Hematology and Clinical Immunology Branch, DIMED University of Padua, Padua, Italy.|Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors: Francesco
authors: F
authors: Piazza
authors: Department of Experimental, Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors: Claudio
authors: C
authors: Agostinelli
authors: Department of Experimental, Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors: Fabio
authors: F
authors: Fuligni
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, DIMED University of Padua, Padua, Italy.
authors: Pietro
authors: P
authors: Benvenuti
authors: Department of Medicine, Hematology and Clinical Immunology Branch, DIMED University of Padua, Padua, Italy.|Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors: Elisa
authors: E
authors: Mandato
authors: Department of Medicine, Hematology and Clinical Immunology Branch, DIMED University of Padua, Padua, Italy.|Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors: Alessandro
authors: A
authors: Casellato
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, DIMED University of Padua, Padua, Italy.
authors: Massimo
authors: M
authors: Rugge
authors: Department of Medicine, Hematology and Clinical Immunology Branch, DIMED University of Padua, Padua, Italy.|Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors: Gianpietro
authors: G
authors: Semenzato
authors: Department of Experimental, Hematopathology and Hematology Sections, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors: Stefano A
authors: SA
authors: Pileri
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018833:Chaperonins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008224:Lymphoma, Follicular / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009287:Naphthyridines / Q000494:pharmacology; D010619:Phenazines; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D009287:Naphthyridines; D010619:Phenazines; D047428:Protein Kinase Inhibitors; C498143:RELA protein, human; D012333:RNA, Messenger; D051996:Transcription Factor RelA; C555142:silmitasertib; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; D018833:Chaperonins
keywords: B-cell; CK2; CX-4945; non-Hodgkin lymphoma