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Clin Cancer Res. 2007 Feb 1;13(3):1019-28.

Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia.

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  • 1Department 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.

Abstract

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.

PMID:
17289898
[PubMed - indexed for MEDLINE]
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