STAT3 pathway is activated in ALK-positive large B-cell lymphoma carrying SQSTM1-ALK rearrangement and provides a possible therapeutic target

Am J Surg Pathol. 2013 May;37(5):780-6. doi: 10.1097/PAS.0b013e318287791f.


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.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Anaplastic Lymphoma Kinase
  • Gene Rearrangement
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Large B-Cell, Diffuse / genetics*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Male
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism*
  • Sequestosome-1 Protein
  • Signal Transduction / physiology*


  • Adaptor Proteins, Signal Transducing
  • SQSTM1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Sequestosome-1 Protein
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases