Abstract
Background: Casein Kinase 2 (CK2) is a Ser/Thr protein kinase that coregulates a great number of signalling pathways in the cell. It is involved in cell cycle regulation and cell proliferation, apoptosis, DNA damage response and gene transcription. Its substrates are numerous kinases and transcription factors. It was found to be upregulated in different tumours, and certain types of leukaemia are very sensitive to its inhibition.
Objective: We analysed the effects of casein kinase 2 inhibition on three leukaemia cell lines of B and T cell origin: Jurkat, a T cell line, CLL, a chronic B lymphocytic leukaemia cell line and 697, a pre-B acute lymphocytic leukaemia cell line. Besides cell proliferation and cytotoxicity analysis, the aim was to investigate the influence of CK2 inhibition on elements of the Notch signalling pathway. Notch signalling has an important role in blood cell differentiation, and CK2 regulates Ikaros, a tumour suppressor interfering with Notch signalling. Methods: B and T leukaemia cells were treated with different concentrations of the CK2 inhibitor, CX-4945, for 6 days, and cell viability and proliferation were determined by Trypan Blue Exclusion Method. Analysis of gene expression was performed by RT-qPCR. Results: All three cell lines were sensitive to CK2 inhibition and among them, 697 cells had two times lower IC50. In Jurkat and CLL cells changes in c-Myc and Notch pathway gene expression were found. Conclusion: As CK2 is involved in numerous signalling circuits, we concluded that each cell type could have a cell-specific response in gene expression.Keywords: Casein kinase 2, CX-4945, lymphocytes, Notch, Ikaros, leukaemia cell line.
Graphical Abstract
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