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Article: Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia

TitleEpigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia
Authors
Issue Date2008
PublisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
Citation
Journal Of Clinical Pathology, 2008, v. 61 n. 11, p. 1214-1219 How to Cite?
AbstractBackground: Wnt signalling has recently been implicated in the pathogenesis of cancer. Methods: This study investigated the activity of Wnt signalling in peripheral blood chronic lymphocytic leukaemia (CLL) lymphocytes, and the methylation status of seven soluble Wnt antagonist genes, including WIF1, DKK3, APC, SFRP1 SFRP2, SFRP4 and SFRP5. by using methylation-specific PCR in the peripheral blood CLL lymphocytes and bone marrow samples of patients with CLL at diagnosis. Results: In the peripheral blood CLL lymphocytes, constitutive activation of Wnt signalling was detected, associated with hypermethylation of the soluble Wnt inhibitor genes. In the diagnostic CLL marrow samples, methylation of the seven genes was detected in up to 36.4% of samples. Moreover, 23 (52.3%) patients had methylation of at least one of the seven genes, of whom 14 (60.8%) had methylation of two or more Wnt inhibitor genes. Apart from an association of advanced age with DKK3 methylation, there was no association of gene hypermethylation with either clinical characteristics (including age, gender, lymphocyte count at diagnosis, Rai stage and poor-risk karyotype) or survival. Conclusion: Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.
Persistent Identifierhttp://hdl.handle.net/10722/59309
ISSN
2015 Impact Factor: 2.912
2015 SCImago Journal Rankings: 1.260
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2010-05-31T03:47:27Z-
dc.date.available2010-05-31T03:47:27Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Clinical Pathology, 2008, v. 61 n. 11, p. 1214-1219en_HK
dc.identifier.issn0021-9746en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59309-
dc.description.abstractBackground: Wnt signalling has recently been implicated in the pathogenesis of cancer. Methods: This study investigated the activity of Wnt signalling in peripheral blood chronic lymphocytic leukaemia (CLL) lymphocytes, and the methylation status of seven soluble Wnt antagonist genes, including WIF1, DKK3, APC, SFRP1 SFRP2, SFRP4 and SFRP5. by using methylation-specific PCR in the peripheral blood CLL lymphocytes and bone marrow samples of patients with CLL at diagnosis. Results: In the peripheral blood CLL lymphocytes, constitutive activation of Wnt signalling was detected, associated with hypermethylation of the soluble Wnt inhibitor genes. In the diagnostic CLL marrow samples, methylation of the seven genes was detected in up to 36.4% of samples. Moreover, 23 (52.3%) patients had methylation of at least one of the seven genes, of whom 14 (60.8%) had methylation of two or more Wnt inhibitor genes. Apart from an association of advanced age with DKK3 methylation, there was no association of gene hypermethylation with either clinical characteristics (including age, gender, lymphocyte count at diagnosis, Rai stage and poor-risk karyotype) or survival. Conclusion: Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.en_HK
dc.languageengen_HK
dc.publisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/en_HK
dc.relation.ispartofJournal of Clinical Pathologyen_HK
dc.rightsJournal of Clinical Pathology. Copyright © B M J Publishing Group.en_HK
dc.titleEpigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9746&volume=61&issue=11&spage=1214&epage=9&date=2008&atitle=Epigenetic+dysregulation+of+the+Wnt+signalling+pathway+in+chronic+lymphocytic+leukaemiaen_HK
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.emailPang, R: robertap@hkucc.hku.hken_HK
dc.identifier.emailLiang, R: rliang@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1136/jcp.2008.060152en_HK
dc.identifier.scopuseid_2-s2.0-56049111627en_HK
dc.identifier.hkuros158553en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56049111627&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1214en_HK
dc.identifier.epage1219en_HK
dc.identifier.isiWOS:000260425100010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK

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