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, YL1 2
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
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
DOIhttp://dx.doi.org/10.1182/blood-2003-06-2007
ISI Accession Number IDWOS:000222001700048
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
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
Author Affiliations
  1. The University of Hong Kong
  2. Queen Mary Hospital Hong Kong