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

Jinseok Kim, In Eom Ju, June Won Cheong, Jin Choi Ae, Koo Lee Jin, Ick Yang Woo, Hong Min Yoo

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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 (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.

Original languageEnglish
Pages (from-to)1019-1028
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number3
DOIs
Publication statusPublished - 2007 Feb 1

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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