Multiple myeloma cell survival relies on high activity of protein kinase CK2.
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-alpha-dependent I kappaB alpha degradation and NF-kappaB-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.
Piazza
Francesco A
FA
Department of Clinical and Experimental Medicine, Hematology-Immunology Division, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Ruzzene
Maria
M
Gurrieri
Carmela
C
Montini
Barbara
B
Bonanni
Luca
L
Chioetto
Gino
G
Di Maira
Giovanni
G
Barbon
Francesca
F
Cabrelle
Anna
A
Zambello
Renato
R
Adami
Fausto
F
Trentin
Livio
L
Pinna
Lorenzo A
LA
Semenzato
Gianpietro
G