Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6

Aberrant activities of JAK/STAT signaling pathways have been observed in several hematologic malignancies. Here, we show high expression of JAK2 in the tumor cells of lymphocyte-predominant Hodgkin lymphoma in 85% of cases and activation of JAK2 in 39% of cases. STAT6, which is a target of JAK2, was...

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Bibliographic Details
Published in:Blood 2007-11, Vol.110 (9), p.3387-3390
Main Authors: Mottok, Anja, Renné, Christoph, Willenbrock, Klaus, Hansmann, Martin-Leo, Bräuninger, Andreas
Format: Article
Language:English
Subjects:
B-Lymphocytes - pathology
Gene Expression Regulation, Neoplastic
Genetic Testing
Hodgkin Disease - genetics
Humans
Janus Kinase 2 - genetics
Mutation
STAT6 Transcription Factor - metabolism
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins - genetics
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Summary:Aberrant activities of JAK/STAT signaling pathways have been observed in several hematologic malignancies. Here, we show high expression of JAK2 in the tumor cells of lymphocyte-predominant Hodgkin lymphoma in 85% of cases and activation of JAK2 in 39% of cases. STAT6, which is a target of JAK2, was activated in 50% of the cases. SOCS1 controls JAK2 activity and degradation. Mutations in SOCS1 of either somatic or germ-line origin were observed in micromanipulated tumor cells of 50% of cases. Most mutations truncated SOCS1 or caused replacement of amino acids in functional important regions. Activating mutations in exon 12 of JAK2, which are frequent in myeloproliferative diseases, were not observed. In lymphocyte-predominant Hodgkin lymphoma SOCS1 function may thus be frequently impaired by mutations, and this may contribute to high JAK2 expression and activation of the JAK2/STAT6 pathway.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-03-082511