ALCL is one of the most common form of NHL. ALCL has been separated in two distinct entities based on the presence or absence of translocations affecting ALK gene. The aim of this project is to demonstrate that ALK+ and ALK- subsets can definitively be considered different entities. ALK- ALCL samples have a more perturbated and complex profile. Among all the ALCLs, the most common losses affected 17p13.3-p12 (TP53, 25%) and 6q21 (PRDM1, 19%). PRDM1 was inactivated in 12/31 (39%) and in 1/33 (3%) of clinical specimens derived from ALK- and ALK+ ALCL respectively, in 4/7 (57%) ALCL cell lines. We perform gain-of-function experiments in order to unravel the function of BLIMP1 loss in ALCL pathogenesis. After the re-expression of PRDM1, ALCL cells underwent proliferation arrest, with a concomitant moderate increase in the percentage of apoptotic cells and an arrest in cell cycle, suggesting a tumor suppressor role for BLIMP1.