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Article: SOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway

TitleSOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathway
Authors
Issue Date2004
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2004, v. 103 n. 12, p. 4630-4635 How to Cite?
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′ 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.
Persistent Identifierhttp://hdl.handle.net/10722/76236
ISSN
2013 Impact Factor: 9.775
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorFung, TKen_HK
dc.contributor.authorCheung, WCen_HK
dc.contributor.authorLiang, Ren_HK
dc.contributor.authorKwong, YLen_HK
dc.date.accessioned2010-09-06T07:19:04Z-
dc.date.available2010-09-06T07:19:04Z-
dc.date.issued2004en_HK
dc.identifier.citationBlood, 2004, v. 103 n. 12, p. 4630-4635en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76236-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshBone Marrow Cells - pathologyen_HK
dc.subject.meshCarrier Proteins - metabolismen_HK
dc.subject.meshDNA Primersen_HK
dc.subject.meshDNA-Binding Proteins - physiologyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntracellular Signaling Peptides and Proteinsen_HK
dc.subject.meshJanus Kinase 1en_HK
dc.subject.meshMaleen_HK
dc.subject.meshMethylationen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMultiple Myeloma - physiopathologyen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshProtein Tyrosine Phosphatase, Non-Receptor Type 6en_HK
dc.subject.meshProtein Tyrosine Phosphatases - metabolismen_HK
dc.subject.meshProtein-Tyrosine Kinases - metabolismen_HK
dc.subject.meshRepressor Proteins - metabolismen_HK
dc.subject.meshSTAT1 Transcription Factoren_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshSuppressor of Cytokine Signaling Proteinsen_HK
dc.subject.meshTrans-Activators - physiologyen_HK
dc.titleSOCS1 and SHP1 hypermethylation in multiple myeloma: Implications for epigenetic activation of the Jak/STAT pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-4971&volume=103&spage=4630&epage=4635&date=2004&atitle=SOCS1+and+SHP1+Hypermethylation+in+Multiple+Myeloma:+Implications+for+Epigenetic+Activation+of+the+Jak/STAT+pathwayen_HK
dc.identifier.emailChim, CS:jcschim@hku.hken_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1182/blood-2003-06-2007en_HK
dc.identifier.pmid14976049en_HK
dc.identifier.scopuseid_2-s2.0-2942584857en_HK
dc.identifier.hkuros88708en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2942584857&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume103en_HK
dc.identifier.issue12en_HK
dc.identifier.spage4630en_HK
dc.identifier.epage4635en_HK
dc.identifier.isiWOS:000222001700048-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridFung, TK=54389057000en_HK
dc.identifier.scopusauthoridCheung, WC=36934683800en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK

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