CK2 kinase is essential for interleukin-7-mediated proliferation of leukemic T cells

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CK2 kinase is essential for interleukin-7-mediated proliferation of leukemic T cells

Wednesday, 16.11.2016

In a recently published study the investigators revealed a crosstalk between two oncogenic pathways, involved in T-cell acute lymphoblastic leekemia (T-ALL): the protein kinase CK2 physically interacts with the interleukin-7 receptor (IL-7R) and is indispensable for optimal signal transduction mediated by IL-7 binding to IL-7R in T-ALL cells. In the absence of CK2 activation, IL-7 is no longer able to mediate viability, cell cycle progression, and proliferation. Pharmacological inhibitors of CK2 may have a broad impact against T-ALL.

 

Authors and Affiliations:

Alice Melão, Maureen Spit, Bruno A. Cardoso, João T. Barata

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

 

Abstract:

Interleukin 7 (IL-7) and its receptor (IL-7R) are essential for normal T-cell development and homeostasis, whereas excessive IL-7/IL-7R-mediated signaling promotes leukemogenesis. Protein kinase CK2 is overexpressed and hyperactivated in cancer, including T-cell acute lymphoblastic leukemia (T-ALL). Here, we show that while IL-7 had a minor but significant positive effect on CK2 activity in T-ALL cells, CK2 activity was mandatory for optimal IL-7/IL-7R-mediated signaling. CK2 pharmacological inhibition abrogated STAT5 and PI3K/Akt pathway activation triggered by IL-7 or by mutational activation of IL-7Rα. By contrast, forced expression of CK2 augmented IL-7 signaling in HEK293T cells reconstituted with the IL-7R machinery. CK2 inactivation prevented IL-7-induced Bcl-2 upregulation, maintenance of mitochondrial homeostasis and viability of T-ALL cell lines and primary leukemia cells collected from patients at diagnosis. CK2 inhibition further abrogated IL-7-mediated cell growth and upregulation of the transferrin receptor, and blocked cyclin A and E upregulation and T-ALL cell cycle progression. Notably, CK2 was also required for the viability of mutant IL-7R-expressing T-ALL cells. Overall, our study identifies CK2 as a major player in the effects of IL-7 and IL-7R in T-ALL. This further highlights the potential relevance of targeting CK2 in this malignancy.

 

Journal: Haematologica

 

Link: http://www.haematologica.org/content/101/11/1368.long