title: STAT3 pathway is activated in ALK-positive large B-cell lymphoma carrying SQSTM1-ALK rearrangement and provides a possible therapeutic target.
abstract: ALK-positive large B-cell lymphomas usually harbor clathrin (CLTC)-ALK rearrangement or, more rarely, nucleophosmin (NPM)-ALK fusion gene. Here we report a large B-cell lymphoma with a peculiar pattern of diffuse and cytoplasmic immunohistochemical staining and carrying sequestosome 1 (SQSTM1)-ALK rearrangement, identified by reverse transcription polymerase chain reaction analysis and Rapid Amplification of cDNA Ends analysis and confirmed by fluorescence in situ hybridization with specific dual-color fusion probes. The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis. Consequently, STAT3 inhibition provides a possible therapeutic target also for lymphomas with SQSTM1-ALK variant translocation.
authors.affiliation: Department of Pathology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Emanuele S G
authors.initials: ES
authors.lastname: d'Amore
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Andrea
authors.initials: A
authors.lastname: Menin
authors.forename: Barbara
authors.initials: B
authors.lastname: Famengo
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonvini
authors.forename: Elena
authors.initials: E
authors.lastname: Lazzari
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071456:Sequestosome-1 Protein; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases