Table of Contents
Journal of Signal Transduction
Volume 2012 (2012), Article ID 123253, 14 pages
http://dx.doi.org/10.1155/2012/123253
Review Article

NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases

1Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2E1
2Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada T6G 2B7

Received 21 March 2012; Accepted 28 April 2012

Academic Editor: Rudi Beyaert

Copyright © 2012 Joel D. Pearson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Anaplastic lymphoma kinase (ALK) was first identified in 1994 with the discovery that the gene encoding for this kinase was involved in the t(2;5)(p23;q35) chromosomal translocation observed in a subset of anaplastic large cell lymphoma (ALCL). The NPM-ALK fusion protein generated by this translocation is a constitutively active tyrosine kinase, and much research has focused on characterizing the signalling pathways and cellular activities this oncoprotein regulates in ALCL. We now know about the existence of nearly 20 distinct ALK translocation partners, and the fusion proteins resulting from these translocations play a critical role in the pathogenesis of a variety of cancers including subsets of large B-cell lymphomas, nonsmall cell lung carcinomas, and inflammatory myofibroblastic tumours. Moreover, the inhibition of ALK has been shown to be an effective treatment strategy in some of these malignancies. In this paper we will highlight malignancies where ALK translocations have been identified and discuss why ALK fusion proteins are constitutively active tyrosine kinases. Finally, using ALCL as an example, we will examine three key signalling pathways activated by NPM-ALK that contribute to proliferation and survival in ALCL.