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Article: SOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway
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TitleSOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway
 
AuthorsChim, CS2
Fung, TK2
Cheung, WC2
Liang, R2
Kwong, YL2 1
 
Issue Date2004
 
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
CitationBlood, 2004, v. 103 n. 12, p. 4630-4635 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2003-06-2007
 
AbstractSOCS1 and SHP1 negatively regulate the Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway. The role of promoter hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma was investigated. The methylation-specific polymerase chain reaction (MSP) was used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For SOCS1, MSP primers 3′ to the translation start site were unreliable and gave positive results in normal controls. However, primers in the 5′ promoter region were specific, although no myeloma samples showed methylation. For SHP1, 27 of 34 (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance of SHP1 methylation was investigated in the U266 human myeloma line. U266 contained completely methylated SHP1. Furthermore, there was constitutive STAT3 phosphorylation. Treatment with 5-azacytidine led to progressive demethylation of SHP1 on days 2 to 5, with consequent increasing reexpression of SHP1 as shown by reverse transcription-polymerase chain reaction (RT-PCR). Concomitant with increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so that by day 5 phosphorylated STAT3 was barely detectable. The overall survivals of patients with and without SHP1 methylation were similar. SHP1 methylation leading to epigenetic activation of the Jak/STAT pathway might have a tentative role in the pathogenesis of myeloma, which should be further confirmed by functional studies in primary myeloma samples. © 2004 by The American Society of Hematology.
 
ISSN0006-4971
2013 Impact Factor: 9.775
 
DOIhttp://dx.doi.org/10.1182/blood-2003-06-2007
 
ISI Accession Number IDWOS:000222001700048
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChim, CS
 
dc.contributor.authorFung, TK
 
dc.contributor.authorCheung, WC
 
dc.contributor.authorLiang, R
 
dc.contributor.authorKwong, YL
 
dc.date.accessioned2010-09-06T07:19:04Z
 
dc.date.available2010-09-06T07:19:04Z
 
dc.date.issued2004
 
dc.description.abstractSOCS1 and SHP1 negatively regulate the Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway. The role of promoter hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma was investigated. The methylation-specific polymerase chain reaction (MSP) was used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For SOCS1, MSP primers 3′ to the translation start site were unreliable and gave positive results in normal controls. However, primers in the 5′ promoter region were specific, although no myeloma samples showed methylation. For SHP1, 27 of 34 (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance of SHP1 methylation was investigated in the U266 human myeloma line. U266 contained completely methylated SHP1. Furthermore, there was constitutive STAT3 phosphorylation. Treatment with 5-azacytidine led to progressive demethylation of SHP1 on days 2 to 5, with consequent increasing reexpression of SHP1 as shown by reverse transcription-polymerase chain reaction (RT-PCR). Concomitant with increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so that by day 5 phosphorylated STAT3 was barely detectable. The overall survivals of patients with and without SHP1 methylation were similar. SHP1 methylation leading to epigenetic activation of the Jak/STAT pathway might have a tentative role in the pathogenesis of myeloma, which should be further confirmed by functional studies in primary myeloma samples. © 2004 by The American Society of Hematology.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationBlood, 2004, v. 103 n. 12, p. 4630-4635 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2003-06-2007
 
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2003-06-2007
 
dc.identifier.epage4635
 
dc.identifier.hkuros88708
 
dc.identifier.isiWOS:000222001700048
 
dc.identifier.issn0006-4971
2013 Impact Factor: 9.775
 
dc.identifier.issue12
 
dc.identifier.openurl
 
dc.identifier.pmid14976049
 
dc.identifier.scopuseid_2-s2.0-2942584857
 
dc.identifier.spage4630
 
dc.identifier.urihttp://hdl.handle.net/10722/76236
 
dc.identifier.volume103
 
dc.languageeng
 
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBlood
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshAged, 80 and over
 
dc.subject.meshBase Sequence
 
dc.subject.meshBone Marrow Cells - pathology
 
dc.subject.meshCarrier Proteins - metabolism
 
dc.subject.meshDNA Primers
 
dc.subject.meshDNA-Binding Proteins - physiology
 
dc.subject.meshFemale
 
dc.subject.meshHumans
 
dc.subject.meshIntracellular Signaling Peptides and Proteins
 
dc.subject.meshJanus Kinase 1
 
dc.subject.meshMale
 
dc.subject.meshMethylation
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMolecular Sequence Data
 
dc.subject.meshMultiple Myeloma - physiopathology
 
dc.subject.meshPolymerase Chain Reaction
 
dc.subject.meshProtein Tyrosine Phosphatase, Non-Receptor Type 6
 
dc.subject.meshProtein Tyrosine Phosphatases - metabolism
 
dc.subject.meshProtein-Tyrosine Kinases - metabolism
 
dc.subject.meshRepressor Proteins - metabolism
 
dc.subject.meshSTAT1 Transcription Factor
 
dc.subject.meshSignal Transduction
 
dc.subject.meshSuppressor of Cytokine Signaling Proteins
 
dc.subject.meshTrans-Activators - physiology
 
dc.titleSOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway
 
dc.typeArticle
 
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<description.abstract>SOCS1 and SHP1 negatively regulate the Janus kinase/signal transducer and activator of transcription (Jak/STAT) signaling pathway. The role of promoter hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma was investigated. The methylation-specific polymerase chain reaction (MSP) was used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For SOCS1, MSP primers 3&#8242; to the translation start site were unreliable and gave positive results in normal controls. However, primers in the 5&#8242; promoter region were specific, although no myeloma samples showed methylation. For SHP1, 27 of 34 (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance of SHP1 methylation was investigated in the U266 human myeloma line. U266 contained completely methylated SHP1. Furthermore, there was constitutive STAT3 phosphorylation. Treatment with 5-azacytidine led to progressive demethylation of SHP1 on days 2 to 5, with consequent increasing reexpression of SHP1 as shown by reverse transcription-polymerase chain reaction (RT-PCR). Concomitant with increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so that by day 5 phosphorylated STAT3 was barely detectable. The overall survivals of patients with and without SHP1 methylation were similar. SHP1 methylation leading to epigenetic activation of the Jak/STAT pathway might have a tentative role in the pathogenesis of myeloma, which should be further confirmed by functional studies in primary myeloma samples. &#169; 2004 by The American Society of Hematology.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Queen Mary Hospital Hong Kong