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Article: Methylation of p15 and p16 genes in adult acute leukemia: Lack of prognostic significance

TitleMethylation of p15 and p16 genes in adult acute leukemia: Lack of prognostic significance
Authors
Issue Date2001
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2001, v. 91 n. 12, p. 2222-2229 How to Cite?
AbstractBACKGROUND. Gene-promoter methylation is an epigenetic mechanism of transcription inactivation. In this study, the authors investigated the frequency and prognostic significance of p15 and p16 gene methylation in adult acute leukemia. METHOD. The methylation-specific polymerase chain reaction (MS-PCR) was used to analyze p15 and p16 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML). RESULTS. At presentation, 93% of cases of AML (8 of 8 M1, 10 of 11 M2, 2 of 2 M4, 5 of 6 M5, and 2 of 2 M6; French-American-British classification system) showed p15 methylation, but none showed p16 methylation. In ALL, 57% (5 of 8 T-ALL, 16 of 30 common-ALL, 6 of 7 pre-B ALL, and 1 of 4 early B-precursor ALL) showed p15 methylation. Only 6% showed p16 methylation, all of whom had concomitant p15 methylation. One patient acquired p16 methylation during relapse. In 23 ALL karyotyped cases, p15 methylation was found in 6 of 9 cases with normal karyotype, 3 of 7 cases with the Philadelphia chromosome, 3 of 5 cases with complex, 1 with hyperdiploidy, and 1 with trisomy 21. Three more cases with unsuccessful karyotyping but bcr/abl fusion showed p15 methylation as well. Five ALL patients were tested serially for minimal residual disease (MRD) with MS-PCR that has a sensitivity of 10-4 to 10-5. All showed continuous positive MS-PCR that heralded hematologic relapse. The prognostic significance of p15 methylation was tested in ALL patients, showing no impact on complete remission, 5-year overall survival, or 5-year disease-free survival. CONCLUSION. Gene methylation of p15, but not p16, is frequent in adult acute leukemias. Methylation of p15 at diagnosis was of no prognostic significance in ALL but may be useful for monitoring MRD. © 2001 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/162555
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_US
dc.contributor.authorTam, CYYen_US
dc.contributor.authorLiang, Ren_US
dc.contributor.authorKwong, YLen_US
dc.date.accessioned2012-09-05T05:21:06Z-
dc.date.available2012-09-05T05:21:06Z-
dc.date.issued2001en_US
dc.identifier.citationCancer, 2001, v. 91 n. 12, p. 2222-2229en_US
dc.identifier.issn0008-543Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/162555-
dc.description.abstractBACKGROUND. Gene-promoter methylation is an epigenetic mechanism of transcription inactivation. In this study, the authors investigated the frequency and prognostic significance of p15 and p16 gene methylation in adult acute leukemia. METHOD. The methylation-specific polymerase chain reaction (MS-PCR) was used to analyze p15 and p16 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML). RESULTS. At presentation, 93% of cases of AML (8 of 8 M1, 10 of 11 M2, 2 of 2 M4, 5 of 6 M5, and 2 of 2 M6; French-American-British classification system) showed p15 methylation, but none showed p16 methylation. In ALL, 57% (5 of 8 T-ALL, 16 of 30 common-ALL, 6 of 7 pre-B ALL, and 1 of 4 early B-precursor ALL) showed p15 methylation. Only 6% showed p16 methylation, all of whom had concomitant p15 methylation. One patient acquired p16 methylation during relapse. In 23 ALL karyotyped cases, p15 methylation was found in 6 of 9 cases with normal karyotype, 3 of 7 cases with the Philadelphia chromosome, 3 of 5 cases with complex, 1 with hyperdiploidy, and 1 with trisomy 21. Three more cases with unsuccessful karyotyping but bcr/abl fusion showed p15 methylation as well. Five ALL patients were tested serially for minimal residual disease (MRD) with MS-PCR that has a sensitivity of 10-4 to 10-5. All showed continuous positive MS-PCR that heralded hematologic relapse. The prognostic significance of p15 methylation was tested in ALL patients, showing no impact on complete remission, 5-year overall survival, or 5-year disease-free survival. CONCLUSION. Gene methylation of p15, but not p16, is frequent in adult acute leukemias. Methylation of p15 at diagnosis was of no prognostic significance in ALL but may be useful for monitoring MRD. © 2001 American Cancer Society.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_US
dc.relation.ispartofCanceren_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAged, 80 And Overen_US
dc.subject.meshCell Cycle Proteinsen_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P15en_US
dc.subject.meshGenes, P16 - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukemia, Myeloid, Acute - Genetics - Mortalityen_US
dc.subject.meshMethylationen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeoplasm, Residual - Geneticsen_US
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma - Genetics - Mortalityen_US
dc.subject.meshPrognosisen_US
dc.subject.meshSensitivity And Specificityen_US
dc.subject.meshTranscription Factors - Geneticsen_US
dc.subject.meshTranscriptional Activationen_US
dc.subject.meshTumor Suppressor Proteinsen_US
dc.titleMethylation of p15 and p16 genes in adult acute leukemia: Lack of prognostic significanceen_US
dc.typeArticleen_US
dc.identifier.emailChim, CS:jcschim@hku.hken_US
dc.identifier.emailLiang, R:rliang@hku.hken_US
dc.identifier.emailKwong, YL:ylkwong@hku.hken_US
dc.identifier.authorityChim, CS=rp00408en_US
dc.identifier.authorityLiang, R=rp00345en_US
dc.identifier.authorityKwong, YL=rp00358en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/1097-0142(20010615)91:12<2222::AID-CNCR1252>3.0.CO;2-Ren_US
dc.identifier.pmid11413509-
dc.identifier.scopuseid_2-s2.0-0035876192en_US
dc.identifier.hkuros60296-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035876192&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume91en_US
dc.identifier.issue12en_US
dc.identifier.spage2222en_US
dc.identifier.epage2229en_US
dc.identifier.isiWOS:000169348200003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChim, CS=7004597253en_US
dc.identifier.scopusauthoridTam, CYY=10045311200en_US
dc.identifier.scopusauthoridLiang, R=26643224900en_US
dc.identifier.scopusauthoridKwong, YL=7102818954en_US

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