Alterations of negative regulators of cytokine signalling in immunodeficiency-related non-Hodgkin lymphoma

Daniela Capello; Annunziata Gloghini; Gianluca Baldanzi; Maurizio Martini; Clara Deambrogi; Marco Lucioni; Daniela Piranda; Rosella Famà; Andrea Graziani; Michele Spina; Umberto Tirelli; Marco Paulli; Luigi Maria Larocca; Gianluca Gaidano; Antonino Carbone; Fabiola Sinigaglia

doi:10.1002/hon.2010

Alterations of negative regulators of cytokine signalling in immunodeficiency-related non-Hodgkin lymphoma

Hematol Oncol. 2013 Mar;31(1):22-8. doi: 10.1002/hon.2010. Epub 2012 Apr 9.

Authors

Daniela Capello¹, Annunziata Gloghini, Gianluca Baldanzi, Maurizio Martini, Clara Deambrogi, Marco Lucioni, Daniela Piranda, Rosella Famà, Andrea Graziani, Michele Spina, Umberto Tirelli, Marco Paulli, Luigi Maria Larocca, Gianluca Gaidano, Antonino Carbone, Fabiola Sinigaglia

Affiliation

¹ Division of Hematology, 'Amedeo Avogadro' University of Eastern Piedmont, Novara, Italy. [email protected]

PMID: 22488585
DOI: 10.1002/hon.2010

Abstract

We investigated immunodeficiency-related non-Hodgkin lymphoma for the presence of molecular alterations affecting negative regulators of the Janus family protein tyrosine kinase/signal transducer and activator of transcription pathway. Protein tyrosine phosphatase, non-receptor type 6/Src homology 2-containing tyrosine phosphatase-1 epigenetic silencing was recurrent in primary effusion lymphoma (100%), and diffuse large B-cell lymphoma (63%), with a higher prevalence in the non-germinal centre subtype, and was associated with the activation of the Janus family protein tyrosine kinase/signal transducer and activator of transcription 3 pathway. Suppressor of cytokine signalling (SOCS)1 and SOCS3 epigenetic silencing were occasionally detected, whereas SOCS1 was frequently mutated in diffuse large B-cell lymphoma and polymorphic post-transplant lymphoproliferative disorders, possibly as a cause of aberrant somatic hypermutation. However, the mutation profile of the coding region of the gene was different from that expected from the aberrant somatic hypermutation process, suggesting that, at least in some cases, SOCS1 mutations may have been selected for their functional activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Clonal Evolution
Cytokines / physiology*
DNA Methylation*
DNA Mutational Analysis
DNA, Neoplasm / genetics
Humans
Immunocompromised Host
Janus Kinases / physiology
Lymphoma, AIDS-Related / genetics*
Lymphoma, AIDS-Related / physiopathology
Lymphoproliferative Disorders / genetics*
Lymphoproliferative Disorders / immunology
Lymphoproliferative Disorders / physiopathology
Mutation
Neoplasm Proteins / genetics*
Neoplasm Proteins / physiology
Organ Transplantation
Postoperative Complications / genetics*
Postoperative Complications / immunology
Postoperative Complications / physiopathology
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics*
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / physiology
Retrospective Studies
STAT Transcription Factors / physiology
Signal Transduction
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / genetics*
Suppressor of Cytokine Signaling Proteins / physiology

Substances

Cytokines
DNA, Neoplasm
Neoplasm Proteins
SOCS1 protein, human
SOCS3 protein, human
STAT Transcription Factors
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Janus Kinases
PTPN6 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 6