Document Detail


Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia.
MedLine Citation:
PMID:  17289898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (CK2alpha) expression in leukemia cell lines and primary leukemic blasts obtained from AML patients. RESULTS: In this study, the expression of CK2alpha 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 CK2alpha-high compared with the CK2alpha-low AML cases (P=0.0252 and P=0.0392, respectively). An induced overexpression of CK2alpha 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. CK2alpha 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 CK2alpha-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 CK2alpha potentially enhanced the sensitivity of U937 cells to the apigenin-induced cell death. Apigenin-induced cell death was significantly higher in CK2alpha-high AML compared with CK2alpha-low AML (P<0.0001) or normal bone marrow samples (P<0.0001). CONCLUSION: These findings strongly suggest protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in AML.
Authors:
Jin Seok Kim; Ju In Eom; June-Won Cheong; Ae Jin Choi; Jin Koo Lee; Woo Ick Yang; Yoo Hong Min
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  13     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-09     Completed Date:  2007-05-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1019-28     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Brain Korea 21 Research Team of Nanobiomaterials for the Cell-Based Implants, Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Antineoplastic Agents / pharmacology*
Apigenin / pharmacology
Casein Kinase II / physiology*
Caspases / metabolism
Catalytic Domain
Cell Line, Tumor
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic*
Humans
Karyotyping
Leukemia, Myeloid, Acute / drug therapy*
Male
Middle Aged
Prognosis*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2 / metabolism
U937 Cells
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Proto-Oncogene Proteins c-bcl-2; 520-36-5/Apigenin; EC 2.7.11.1/Casein Kinase II; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspases

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