Activation status of the JAK/STAT3 pathway in mantle cell lymphoma

Marwan A. Yared, Joseph D. Khoury, L. Jeffrey Medeiros, George Z. Rassidakis, Raymond Lai

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

Abstract

Context. - Signal transducer and activator of transcription 3 (STAT3) is oncogenic, and we previously found evidence of constitutive STAT3 activation in a relatively small number of frozen mantle cell lymphoma (MCL) cell tumors. Objectives. - To comprehensively survey the activation and phosphorylation status of STAT3 in MCL and to assess if STAT3 activation in these tumors is due to cytokine stimulation by examining the phosphorylation and activation status of Janus kinase (JAK), the physiologic activator of STAT3. Design. - We evaluated 43 formalin-fixed, paraffin-embedded MCL tumors using immunohistochemistry and phospho-specific antibodies against STAT3 and JAK. Results. - There were 37 small cell and 6 blastoid cases. There was heterogeneous expression of phospho-STAT3 (pSTAT3), with 23 negative cases (53%), 12 weakly positive cases (28%), and 8 strongly positive cases (19%). JAK3 was the only member detectable in 3 MCL cell lines, and immunoprecipitation data showed a relatively low level of tyrosine phosphorylation of JAK3 in these cells. Using immunohistochemistry, phospho-JAK3 (pJAK3) was detectable in 18 (44%) of 41 MCL tumors examined, and pJAK3 expression correlated with that of pSTAT3 (P = .008). A notable exception to this correlation was seen in the blastoid variant, since 4 (67%) of 6 blastoid cases were pSTAT3 positive but pJAK3 negative. Conclusions. - We have confirmed our previous finding that STAT3 is constitutively activated in MCL tumors, with an overall frequency of 47% in this series. STAT3 activation in the small cell but not the blastoid variant of MCL is likely mediated by JAK3.

Original languageEnglish (US)
Pages (from-to)990-996
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Volume129
Issue number8
StatePublished - Aug 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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