Gene methylation and silencing of SOCS3 in mantle cell lymphoma. (22nd February 2013)

• Record Type: Journal Article
• Authors: Molavi, Ommoleila; Wang, Peng; Zak, Zoulika; Gelebart, Pascal; Belch, Andrew; Lai, Raymond
• Is Part Of: British journal of haematology. Volume 161:Number 3(2013:May)
• Page Start: 348
• Page End: 356
• Publication Date: 2013-02-22
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12262
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" xml:lang="en" id="bjh12262-abs-0001"> <title>Summary</title> <p>The significance of loss of SOCS3, a negative regulator of signalling pathways including those of STAT3 and NF<italic>‐κ</italic>B<italic>, </italic> was examined in mantle cell lymphoma (MCL). The protein expression and gene methylation status of <italic>SOCS3</italic> were detected using immunohistochemistry/Western blots and methylation‐specific polymerase chain reaction, respectively. To evaluate its functional importance, SOCS3 was restored in two SOCS3‐negative MCL cell lines using a lentiviral vector. Loss of SOCS3 protein expression was found in 3/4 MCL cell lines and 18/33 (54·5%) tumours. <italic>SOCS3</italic> was found consistently methylated in cell lines (3/4) and tumours (7/7) negative for SOCS3, and was unmethylated in all SOCS3‐positive cell line (1/1) and tumours (5/5) examined. Treatment of all three SOCS3‐negative cell lines with 2′‐deoxy‐5‐azacytidine restored SOCS3 expression. SOCS3 is biologically important in MCL, as lentiviral transfer of <italic>SOCS3</italic> in SOCS3‐negative cell lines increased their apoptotic activity, downregulated nuclear factor (NF)<italic>‐κ</italic>B‐p65, cyclin D1 (CCND1), BCL2 and BCL‐XL (BCL2L1), and substantially dampened interleukin 10‐induced STAT3 activation. In 19 patients aged ≤69 years at time of diagnosis, we found that those that carried SOCS3‐negative tumours showed a trend toward a worse outcome (<italic>P</italic> = 0·1, log‐rank).</p> </abstract>