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

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  • Author(s): Kim JS;Kim JS; Eom JI; Cheong JW; Choi AJ; Lee JK; Yang WI; Min YH
  • Source:
    Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2007 Feb 01; Vol. 13 (3), pp. 1019-28.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Print ISSN: 1078-0432 (Print) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Denville, NJ : The Association, c1995-
    • Subject Terms:
      Gene Expression Regulation, Neoplastic* ; Prognosis*; Antineoplastic Agents/*pharmacology ; Casein Kinase II/*physiology ; Leukemia, Myeloid, Acute/*drug therapy; Adolescent ; Adult ; Aged ; Apigenin/pharmacology ; Caspases/metabolism ; Catalytic Domain ; Cell Line, Tumor ; Disease-Free Survival ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-bcl-2/metabolism ; U937 Cells
    • 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.
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Proto-Oncogene Proteins c-bcl-2)
      7V515PI7F6 (Apigenin)
      EC 2.7.11.1 (Casein Kinase II)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20070210 Date Completed: 20070504 Latest Revision: 20131121
    • Publication Date:
      20231215
    • Accession Number:
      10.1158/1078-0432.CCR-06-1602
    • Accession Number:
      17289898