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Article: Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma

TitleEpigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma
Authors
Issue Date2007
PublisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
Citation
Journal Of Clinical Pathology, 2007, v. 60 n. 6, p. 664-669 How to Cite?
AbstractAim: To study the role of gene promoter hypermethylation of the putative tumour suppressor genes involved in the death-associated protein (DAP) kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma (MM). Method: DNAs from 55 primary MM marrow samples and myeloma cell lines were analysed for aberrant promoter methylation of DAP kinase, p14 and Apaf-1 genes by methylation-specific polymerase chain reaction (MSP). Result: In the methylated positive control, the sensitivity of M-MSP for DAP kinase was 1 × 10 3. Aberrant hypermethylation of DAP kinase was found in 29/55 (52.7%) primary MM samples, whereas hypermethylation of p14 or Apaf-1 was undetectable in any of the samples tested. 5-Azacytidine treatment of two myeloma cell lines, WL2 and HS-Sultan, led to de-methylation and re-expression of DAP kinase, thereby confirming gene silencing associated with promoter hypermethylation. Hypermethylation of DAP kinase did not correlate with age, sex, paraprotein subtype or Durie-Salmon stage, but negatively affected the overall survival. Conclusion: Of the putative tumour suppressor genes in the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway, only DAP kinase is frequently methylated in MM, which is associated with gene silencing and might be of prognostic significance, p14 and Apaf-1 were not methylated in MM.
Persistent Identifierhttp://hdl.handle.net/10722/57537
ISSN
2015 Impact Factor: 2.912
2015 SCImago Journal Rankings: 1.260
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorLiang, Ren_HK
dc.contributor.authorFung, TKen_HK
dc.contributor.authorChoi, CLen_HK
dc.contributor.authorKwong, YLen_HK
dc.date.accessioned2010-04-12T01:39:22Z-
dc.date.available2010-04-12T01:39:22Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Clinical Pathology, 2007, v. 60 n. 6, p. 664-669en_HK
dc.identifier.issn0021-9746en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57537-
dc.description.abstractAim: To study the role of gene promoter hypermethylation of the putative tumour suppressor genes involved in the death-associated protein (DAP) kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma (MM). Method: DNAs from 55 primary MM marrow samples and myeloma cell lines were analysed for aberrant promoter methylation of DAP kinase, p14 and Apaf-1 genes by methylation-specific polymerase chain reaction (MSP). Result: In the methylated positive control, the sensitivity of M-MSP for DAP kinase was 1 × 10 3. Aberrant hypermethylation of DAP kinase was found in 29/55 (52.7%) primary MM samples, whereas hypermethylation of p14 or Apaf-1 was undetectable in any of the samples tested. 5-Azacytidine treatment of two myeloma cell lines, WL2 and HS-Sultan, led to de-methylation and re-expression of DAP kinase, thereby confirming gene silencing associated with promoter hypermethylation. Hypermethylation of DAP kinase did not correlate with age, sex, paraprotein subtype or Durie-Salmon stage, but negatively affected the overall survival. Conclusion: Of the putative tumour suppressor genes in the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway, only DAP kinase is frequently methylated in MM, which is associated with gene silencing and might be of prognostic significance, p14 and Apaf-1 were not methylated in MM.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.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsJournal of clinical pathology. Copyright © B M J Publishing Group.en_HK
dc.subject.meshApoptosis Regulatory Proteins - geneticsen_HK
dc.subject.meshEpigenesis, Geneticen_HK
dc.subject.meshMultiple Myeloma - genetics - pathology - therapyen_HK
dc.subject.meshNeoplasm Proteins - geneticsen_HK
dc.subject.meshTumor Markers, Biological - geneticsen_HK
dc.titleEpigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myelomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9746&volume=60&issue=6&spage=664&epage=669&date=2007&atitle=Epigenetic+dysregulation+of+the+death-associated+protein+kinase/p14/HDM2/p53/Apaf-1+apoptosis+pathway+in+multiple+myelomaen_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.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/jcp.2006.038331en_HK
dc.identifier.pmid17557868-
dc.identifier.pmcidPMC1955062-
dc.identifier.scopuseid_2-s2.0-34250827855en_HK
dc.identifier.hkuros137010-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34250827855&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue6en_HK
dc.identifier.spage664en_HK
dc.identifier.epage669en_HK
dc.identifier.isiWOS:000247125300016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.scopusauthoridFung, TK=54389057000en_HK
dc.identifier.scopusauthoridChoi, CL=8576533600en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK

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