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Antonella Barreca, Elena Lasorsa, Ludovica Riera, Rodolfo Machiorlatti, Roberto Piva, Maurilio Ponzoni, Ivo Kwee, Francesco Bertoni, Pier Paolo Piccaluga, Stefano A Pileri, Giorgio Inghirami and The European T-Cell Lymphoma Study Group

The receptor tyrosine kinases (RTKs) play a critical role, controlling cell proliferation, survival, and differentiation of normal cells. Their pivotal function has been firmly established in the pathogenesis of many cancers as well. The anaplastic lymphoma kinase (ALK), a transmembrane RTK, originally identified in the nucleophosmin (NPM)–ALK chimera of anaplastic large cell lymphoma, has emerged as a novel tumorigenic player in several human cancers. In this review, we describe the expression of the ALK–RTK, its related fusion proteins, and their molecular mechanisms of activation. Novel tailored strategies are briefly illustrated for the treatment of ALK-positive neoplasms.