The anaplastic lymphoma kinase (ALK) gene fuses to the nucleophosmin (NPM) gene 
as a result of a (2;5) translocation associated with a subtype of human lymphoma 
(initially designated anaplastic large cell lymphoma [ALCL] or 
Ki-1/CD30-positive lymphoma). The immunocytochemical detection of NPM-ALK (and 
proteins encoded by other ALK fusion genes) has allowed the definition of a 
tumor entity, "ALK-positive lymphoma" (which shows only partial overlap with 
pathologists' diagnosis of ALCL), to be defined and is invaluable in 
distinguishing this disease from ALK-negative large cell lymphomas. Eight 
variant ALK fusion proteins have been identified. Some are expressed only in 
ALCL, some are found only in the nonhematopoietic neoplasm inflammatory 
myofibroblastic tumor (IMT), and some are present in both types of malignancy. 
The ALK gene is silent in adult tissues except for restricted sites within the 
nervous system (consequently, patients with ALK-positive lymphoma produce 
antibodies to the ALK protein) but is expressed in some neuroblastomas and 
rhabdomyosarcomas. Biochemical studies suggest an anti-apoptotic function of 
NPM-ALK, and this may contribute to oncogenesis. Although ALK-positive lymphomas 
have a generally good prognosis, new therapeutic regimens are still needed for 
patients whose disease is refractory to conventional treatment.