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.
Keywords:
B-cell; CK2; CX-4945; non-Hodgkin lymphoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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B-Lymphocytes / drug effects
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B-Lymphocytes / enzymology*
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B-Lymphocytes / pathology
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Blotting, Western
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Burkitt Lymphoma / enzymology*
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / pathology
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Casein Kinase II / antagonists & inhibitors
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Casein Kinase II / genetics
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Casein Kinase II / metabolism
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation* / drug effects
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Cell Survival / drug effects
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Chaperonins / metabolism
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Dose-Response Relationship, Drug
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Gene Expression Profiling
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Humans
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Lymphoma, Follicular / enzymology*
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Lymphoma, Follicular / genetics
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Lymphoma, Follicular / pathology
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Lymphoma, Large B-Cell, Diffuse / enzymology*
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Lymphoma, Large B-Cell, Diffuse / genetics
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Lymphoma, Large B-Cell, Diffuse / pathology
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Naphthyridines / pharmacology
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Phenazines
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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RNA, Messenger / metabolism
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Retrospective Studies
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Signal Transduction
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Transcription Factor RelA / metabolism
Substances
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Antineoplastic Agents
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CDC37 protein, human
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Cell Cycle Proteins
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Naphthyridines
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Phenazines
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Protein Kinase Inhibitors
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RELA protein, human
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RNA, Messenger
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Transcription Factor RelA
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silmitasertib
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CSNK2A1 protein, human
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Casein Kinase II
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Chaperonins