Anaplastic lymphoma kinase proteins and malignancy

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 huma n lymphoma (initially designated anaplastic large cell lymphoma [ALCL] or K i-1/CD30-positive lymphoma). The immunocytochemical detection of NPM-ALK (a nd proteins encoded by,other ALK fusion genes) has allowed the definition o f 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 v ariant ALK fusion proteins have been identified. Some are expressed only in ALCL, some are found only in the nonhematopoietic neoplasm inflammatory my ofibroblastic tumor (IMT), and some are present in both types of malignancy . The ALK gene is silent in adult tissues except for restricted sites withi n the nervous system (consequently, patients with ALK-positive lymphoma pro duce antibodies to the ALK protein) but Is expressed in some neuroblastomas and rhabdomyosarcomas. Biochemical studies suggest an anti-apoptotic funct ion of NPM-ALK, and this may contribute to oncogenesis. Although ALK-positi ve lymphomas, have a generally good prognosis, new therapeutic regimens are still needed for patients whose disease is refractory to conventional trea tment. (C) 2001 Lippincott Williams & Wilkins, Inc.