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Protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia

 Jin Seok Kim  ;  Ju In Eom  ;  Yoo Hong Min  ;  Woo Ick Yang  ;  Jin Koo Lee  ;  Ae Jin Choi  ;  June-Won Cheong 
 CLINICAL CANCER RESEARCH, Vol.13(3) : 1019-1028, 2007 
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Introduction: Protein kinase CK2 is implicated in cellular proliferation and transformation. However, the clinical and biological significances of CK2 have not been elucidated in acute myeloid leukemia (AML). Experimental Design: We evaluated the biological significances of catalytic subunit of CK2 (CK2α) expression in leukemia cell lines and primary leukemic blasts obtained from AML patients. Results: In this study, the expression of CK2α was elevated in a substantial proportion of AML. In AML patients with normal karyotype, the disease-free survival and overall survival rates were significantly lower in the CK2α-high compared with the CK2α-low AML cases (P = 0.0252 and P = 0.0392, respectively). An induced overexpression of CK2α increased the levels of Ser473 phosphorylated (p)-Akt/protein kinase B (PKB), p-PDK1, pFKHR, p-BAD, Bcl-2, Bcl-xL, Mcl-1, and XIAP. Treatment of U937 cell line and primary AML blasts with selective CK2 inhibitor, tetrabromobenzotriazole or apigenin, reduced the levels of these molecules in a dose-dependent manner. CK2α small interfering RNA treatment also resulted in a down-regulation of p-Akt/PKB and Bcl-2 in U937 cells. Apigenin-induced cell death was preferentially observed in the CK2α-high leukemia cell lines, HL-60 and NB4, which was accompanied by cytoplasmic release of SMAC/DIABLO and proteolytic cleavage of procaspase-9, procaspase-3, procaspase-8, and poly(ADP)ribose polymerase. An induced overexpression of CK2α potentially enhanced the sensitivity of U937 cells to the apigenin-induced cell death. Apigenin-induced cell death was significantly higher in CK2α-high AML compared with CK2α-low AML (P < 0.0001) or normal bone marrow samples (P < 0.0001). Conclusion: These findings strongly suggest protein kinase CK2α as an unfavorable prognostic marker and novel therapeutic target in AML.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Eom, Ju In(엄주인)
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Choi, Ae Jin(최애진)
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