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Article: Methylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients

TitleMethylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patients
Authors
Issue Date2006
PublisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
Citation
Journal Of Clinical Pathology, 2006, v. 59 n. 9, p. 921-926 How to Cite?
AbstractBackground: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2, respectively. Aim: To study the role of methylation in the inactivation of CKI in chronic lymphocytic leukaemia (CLL). Materials and methods: Methylation-specific polymerase chain reaction was carried out on DNA obtained from the bone marrow of 56 newly diagnosed patients with CLL. Results: Similar demographic features and clinical outcome were observed in our patients when compared with Caucasian patients, including an indolent clinical course (10-year overall survival 51%) and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12 and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%) CLL samples harboured concurrent methylation of both p15 and p16. Apart from an association of p16 methylation with higher presenting leucocyte count (64.5×10 9/l in methylated p16 and 16.0×10 9/l in unmethylated p16 patients; p = 0.016), there was no association between p15 and p16 methylation and age, sex and Rai stage. No difference was observed in the overall survival for patients with and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4 (7.1%) patients, methylation of p21 and p27 was uniformly absent. Conclusion: p15 and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP family, were targeted by methylation in CLL. p16 methylation was associated with a higher lymphocyte count at presentation. This is the first comprehensive study of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in Chinese patients with CLL.
Persistent Identifierhttp://hdl.handle.net/10722/45011
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.authorFung, TKen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorLau, JSen_HK
dc.contributor.authorLaw, Men_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2007-10-30T06:15:35Z-
dc.date.available2007-10-30T06:15:35Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Clinical Pathology, 2006, v. 59 n. 9, p. 921-926en_HK
dc.identifier.issn0021-9746en_HK
dc.identifier.urihttp://hdl.handle.net/10722/45011-
dc.description.abstractBackground: INK4 (p15, p16, p18 and p19) and CIP/KIP (p21, p27 and p57) are two families of cyclin-dependent kinase inhibitors (CKI) targeting CDK4/6 and CDK2, respectively. Aim: To study the role of methylation in the inactivation of CKI in chronic lymphocytic leukaemia (CLL). Materials and methods: Methylation-specific polymerase chain reaction was carried out on DNA obtained from the bone marrow of 56 newly diagnosed patients with CLL. Results: Similar demographic features and clinical outcome were observed in our patients when compared with Caucasian patients, including an indolent clinical course (10-year overall survival 51%) and advanced Rai stage (p = 0.006), and a high-risk karyotype such as trisomy 12 and complex aberrations (p = 0.03). In the INK4 family, methylation in p15 and p16 occurred in 20 (35.7%) and 8 (14.3%) patients, respectively. In all, 5 (8.9%) CLL samples harboured concurrent methylation of both p15 and p16. Apart from an association of p16 methylation with higher presenting leucocyte count (64.5×10 9/l in methylated p16 and 16.0×10 9/l in unmethylated p16 patients; p = 0.016), there was no association between p15 and p16 methylation and age, sex and Rai stage. No difference was observed in the overall survival for patients with and without p15 and p16 methylation. By contrast, p18 and Rb were unmethylated in all samples. In the CIP/KIP family, apart from infrequent methylation of p57 in 4 (7.1%) patients, methylation of p21 and p27 was uniformly absent. Conclusion: p15 and, less frequently, p16 of the INK4 family of CKI, instead of the CIP or KIP family, were targeted by methylation in CLL. p16 methylation was associated with a higher lymphocyte count at presentation. This is the first comprehensive study of the epigenetic dysregulation of the INK4 and CIP/KIP families of CKI in Chinese patients with CLL.en_HK
dc.format.extent1138183 bytes-
dc.format.extent1834 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypetext/plain-
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.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCyclin-Dependent Kinase Inhibitor Proteins - geneticsen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA, Neoplasm - geneticsen_HK
dc.subject.meshLeukemia, Lymphocytic, Chronic - geneticsen_HK
dc.subject.meshPolymerase Chain Reaction - methodsen_HK
dc.titleMethylation of INK4 and CIP/KIP families of cyclin-dependent kinase inhibitor in chronic lymphocytic leukaemia in Chinese patientsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9746&volume=59&issue=9&spage=921&epage=926&date=2006&atitle=Methylation+of+INK4+and+CIP/KIP+families+of+cyclin-dependent+kinase+inhibitor+in+chronic+lymphocytic+leukaemia+in+Chinese+patientsen_HK
dc.identifier.emailChim, CS:jcschim@hku.hken_HK
dc.identifier.emailLiang, R:rliang@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/jcp.2005.035089en_HK
dc.identifier.pmid16565223-
dc.identifier.pmcidPMC1860467-
dc.identifier.scopuseid_2-s2.0-33748855626en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33748855626&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue9en_HK
dc.identifier.spage921en_HK
dc.identifier.epage926en_HK
dc.identifier.isiWOS:000240042500005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridFung, TK=54389057000en_HK
dc.identifier.scopusauthoridWong, KF=7404759860en_HK
dc.identifier.scopusauthoridLau, JS=36903981300en_HK
dc.identifier.scopusauthoridLaw, M=8663654000en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK

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