Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas

The currently used 2008 World Health Organization classification recognizes two types of systemic anaplastic large T cell lymphoma according to ALK protein expression in tumour cells. First, the 'anaplastic large cell lymphoma, ALK positive' (ALK(+) ALCL) that is characterized by the presence of ALK gene rearrangements and consequent ALK protein expression, and, second, the 'anaplastic large cell lymphoma, ALK negative' (ALK(-) ALCL) that is a provisional entity lacking ALK protein expression but cannot be distinguished morphologically from ALK(+) ALCL. In this review we summarize the current knowledge on the genetic lesions and biological features that underlie the pathogenesis of ALK(+) and the ALK(-) ALCL and that can lead to the use of targeted anti-cancer agents.