Expression of anaplastic lymphoma kinase in non-Hodgkin's lymphomas and other malignant neoplasms. Biological, diagnostic, and clinical implications.
Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation that creates an NPM-ALK fusion gene, defines a distinct type of T/null-cell lymphoma (TCL) within a vastly heterogeneous group of anaplastic large cell lymphomas. Through the translocation mechanism or as a full-length apparently intact protein, ALK also is expressed by a subset of inflammatory myofibroblastic tumors, glioblastomas, diffuse large B-cell lymphomas, and other malignant neoplasms. Owing to the recent progress in understanding its pathogenesis, ALK+ TCL has become a model malignant neoplasm in which morphology-based diagnosis and classification are gradually shifting toward biology-based diagnosis. Several lines of experimental evidence indicate that the ectopically expressed ALK is oncogenic in ALK+ TCL by being constitutively active owing to autophosphorylation and, consequently, by stimulating several critical signal transduction pathways involving phospholipase C-gamma, AKT, and STAT3 (signal transducer and activator of transcription 3). Targeting ALK and, perhaps, its downstream signaling effector proteins represents a promising novel therapeutic approach to ALK+ TCL. Diagnostic implications of the ALK expression in ALK+ TCL and other malignant neoplasms and the related current controversies are discussed.
Dept of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 7.103 Founders, Philadelphia, PA 19104, USA.
Mariusz A
MA
Wasik
D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002471:Cell Transformation, Neoplastic; D002648:Child; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D015398:Signal Transduction / Q000502:physiology*; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases