Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaplastic large-cell lymphoma (ALCL) provides an excellent example of how molecular insights into tumor pathogenesis are influencing and improving tumor classification. ALCL was described initially as a subtype of T-cell/null-cell lymphoma characterized by unusual tumor cell morphology and the expression of CD30. However, it was soon recognized that a subset of ALCLs contained chromosomal translocations involving anaplastic lymphoma kinase (ALK), a novel receptor tyrosine kinase gene. These rearrangements create chimeric genes encoding self-associating, constitutively active ALK fusion proteins that activate a number of downstream effectors, including phospholipase C-gamma, phosphoinositol 3'-kinase, RAS, and signal transducer and activator of transcription proteins, all of which seem potentially important in cellular transformation. Not all tumors classified as ALCLs have ALK rearrangements and, conversely, ALK rearrangements occur in lymphomas of widely varying morphology. Hence, only molecular markers can reliably identify ALK+ ALCL. The importance of doing so is reflected by clinical studies suggesting that ALK+ ALCLs have a significantly better prognosis than other aggressive peripheral T-cell or B-cell lymphomas, including ALK- ALCLs. The unique molecular pathogenesis of ALK+ ALCL is likely to lead to novel therapeutic approaches directed at specific inhibition of ALK or downstream effectors.
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PMID:Molecular biology of anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma. 1220 71

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.
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PMID:Expression of anaplastic lymphoma kinase in non-Hodgkin's lymphomas and other malignant neoplasms. Biological, diagnostic, and clinical implications. 1456 15