cx-4945 has been researched along with Lymphoma--Follicular* in 1 studies
1 other study(ies) available for cx-4945 and Lymphoma--Follicular
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Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.
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. Topics: Antineoplastic Agents; B-Lymphocytes; Blotting, Western; Burkitt Lymphoma; Casein Kinase II; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chaperonins; Dose-Response Relationship, Drug; Gene Expression Profiling; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Naphthyridines; Phenazines; Phosphorylation; Protein Kinase Inhibitors; Retrospective Studies; RNA, Messenger; Signal Transduction; Transcription Factor RelA | 2015 |