Influence of Casein kinase II inhibitor CX-4945 on BCL6-mediated apoptotic signaling in B-ALL in vitro and in vivo

BMC Cancer
Anna RichterCatrin Roolf

Abstract

Casein kinase II (CK2) is involved in multiple tumor-relevant signaling pathways affecting proliferation and apoptosis. CK2 is frequently upregulated in acute B-lymphoblastic leukemia (B-ALL) and can be targeted by the ATP-competitive CK2 inhibitor CX-4945. While reduced proliferation of tumor entities including B-ALL after CX-4945 incubation has been shown in vitro and in vivo, the detailed way of action is unknown. Here, we investigated the influence on the PI3K/AKT and apoptosis cascades in vivo and in vitro for further clarification. A B-ALL xenograft model in NSG mice was used to perform in vivo longitudinal bioluminescence imaging during six day CX-4945 treatment. CX-4945 serum levels were determined at various time points. Flow cytometry of bone marrow and spleen cells was performed to analyze CX-4945-induced effects on tumor cell proliferation and distribution in B-ALL engrafted mice. ALL cells were enriched and characterized by targeted RNA sequencing. In vitro, B-ALL cell lines SEM, RS4;11 and NALM-6 were incubated with CX-4945 and gene expression of apoptosis regulators BCL6 and BACH2 was determined. In B-ALL-engrafted mice, overall tumor cell proliferation and distribution was not significantly influenced by CK2 inh...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Anna RichterChristian Junghanss

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Methods Mentioned

BETA
bioluminescence imaging
flow cytometry
FCS
Assay
PCR
xenograft
bioluminescence
GTPase
methylome sequencing

Software Mentioned

Indigo
Transcriptome Analysis Console ( TAC )
Image Studio Lite
[UNK] Pro
MS PowerPoint
FACSCalibur

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