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

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Piazza FA,Ruzzene M,Gurrieri C,Montini B,Bonanni L,Chioetto G,Di Maira G,Barbon F,Cabrelle A,Zambello R,Adami F,Trentin L,Pinna LA,Semenzato G

doi

10.1182/blood-2005-11-013672

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

1698-707

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2005-11-013672

journal_volume

108

pub_type

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