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 Blood, 1 September 2006, Vol. 108, No. 5, pp. 1698-1707.
Prepublished online as a Blood First Edition Paper on May 9, 2006; DOI 10.1182/blood-2005-11-013672.

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Submitted November 21, 2005
Accepted April 24, 2006

Multiple myeloma cell survival relies on high activity of protein kinase CK2

Francesco A Piazza, Maria Ruzzene, Carmela Gurrieri, Barbara Montini, Luca Bonanni, Gino Chioetto, Giovanni Di Maira, Francesca Barbon, Anna Cabrelle, Renato Zambello, Fausto Adami, Livio Trentin, Lorenzo A Pinna, and Gianpietro Semenzato*

Department of Clinical and Experimental Medicine,Hematology-Immunology Division,University of Padova
Department of Biological Chemistry, University of Padova, Padova, Italy
Venetian Institute of Molecular Medicine, Padova, Italy

* Corresponding author; email: g.semenzato{at}unipd.it.

Casein kinase 2 (CK2) is an ubiquitous cellular serine- threonine kinase that regulates relevant biological processes many of which are dysregulated in malignant plasma cells. Here, we have investigated its role in multiple myeloma (MM). Analysis of MM cell lines and highly purified malignant plasma cells from MM patients revealed higher protein and activity levels of CK2 as compared to controls (normal in vitro generated polyclonal plasma cells and B lymphocytes). The inhibition of CK2 with specific synthetic compounds or by means of RNA interference caused a cytotoxic effect on MM plasma cells that could not be overcome by IL-6 or IGF-I and associated with the activation of the extrinsic and intrinsic caspase cascades. CK2 blockage also lowered the threshold of sensitivity of MM plasma cells to the cytotoxic effect of melphalan. CK2 inhibition also resulted in an impairment of IL-6- dependent STAT3 activation and in a decreased basal and TNF{alpha}-dependent I{kappa}B{alpha} degradation and NF-{kappa}B-driven transcription. Our data show CK2 involved in the pathophysiology of MM, suggesting that it might play a crucial role in controlling survival and sensitivity to chemotherapeutics of malignant plasma cells.


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