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

From the Department of Clinical and Experimental Medicine, Hematology-Immunology Division, and the Department of Biological Chemistry, University of Padova School of Medicine, Padova, Italy; and the Venetian Institute of Molecular Medicine, Padova, Italy.

Casein kinase 2 (CK2) is a ubiquitous cellular serine-threonine kinase that regulates relevant biologic processes, many of which are dysregulated in malignant plasma cells. Here we investigated its role in multiple myeloma (MM). Analysis of MM cell lines and highly purified malignant plasma cells in patients with MM revealed higher protein and CK2 activity levels than in 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 that was associated with the activation of extrinsic and intrinsic caspase cascades. CK2 blockage lowered the sensitivity threshold of MM plasma cells to the cytotoxic effect of melphalan. CK2 inhibition also resulted in impaired IL-6-dependent STAT3 activation and in decreased basal and TNF--dependent IB degradation and NF-B-driven transcription. Our data show that CK2 was 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.