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Article: Aberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemia

TitleAberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemia
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
Citation
Leukemia, 2005, v. 19 n. 12, p. 2241-2246 How to Cite?
AbstractThe retinoic acid receptor alpha (RARA) gene is disrupted by PML/RARA fusion in acute promyelocytic leukemia (APL). The P2 promoter of RARA, controlling the RARα2 isoform, contains an RA-responsive element and may be targeted in APL. To test whether aberrant methylation of P2 was involved, 47 APL at diagnosis, 16 APL at first relapse, 50 acute myeloid leukemia (AML) and 22 acute lymphoblastic leukemia (ALL) were tested by methylation-specific polymerase chain reaction. RARA P2 methylation was highly associated with APL (APL: 25/63 vs AML/ALL: 2/75, P<0.0001). P2 methylation occurred at similar frequencies in APL at diagnosis and relapse, suggesting it was an initiating leukemogenic event. In the APL line NB4, RARα2 was not expressed, with the untranslocated RARA shown to be P2 methylated. 5-Azacytadine treatment of NB4 led to progressive P2 demethylation and re-expression of RARα2, confirming that RARA methylation collaborated with PML/RARA in totally suppressing RARα. In APL, RARA P2 methylation was unrelated to gender, age, presenting leukocyte counts and additional cytogenetic aberrations. For APL patients receiving all-trans retinoic acid for induction, P2 methylation did not affect the complete remission rates and survivals. RARA is the first myeloid-specific transcription factor shown to be dysregulated by both translocation and aberrant methylation. © 2005 Nature Publishing Group All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/77755
ISSN
2015 Impact Factor: 12.104
2015 SCImago Journal Rankings: 5.142
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorWong, SYen_HK
dc.contributor.authorPang, Aen_HK
dc.contributor.authorChu, Pen_HK
dc.contributor.authorLau, JSen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorKwong, YLen_HK
dc.date.accessioned2010-09-06T07:35:22Z-
dc.date.available2010-09-06T07:35:22Z-
dc.date.issued2005en_HK
dc.identifier.citationLeukemia, 2005, v. 19 n. 12, p. 2241-2246en_HK
dc.identifier.issn0887-6924en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77755-
dc.description.abstractThe retinoic acid receptor alpha (RARA) gene is disrupted by PML/RARA fusion in acute promyelocytic leukemia (APL). The P2 promoter of RARA, controlling the RARα2 isoform, contains an RA-responsive element and may be targeted in APL. To test whether aberrant methylation of P2 was involved, 47 APL at diagnosis, 16 APL at first relapse, 50 acute myeloid leukemia (AML) and 22 acute lymphoblastic leukemia (ALL) were tested by methylation-specific polymerase chain reaction. RARA P2 methylation was highly associated with APL (APL: 25/63 vs AML/ALL: 2/75, P<0.0001). P2 methylation occurred at similar frequencies in APL at diagnosis and relapse, suggesting it was an initiating leukemogenic event. In the APL line NB4, RARα2 was not expressed, with the untranslocated RARA shown to be P2 methylated. 5-Azacytadine treatment of NB4 led to progressive P2 demethylation and re-expression of RARα2, confirming that RARA methylation collaborated with PML/RARA in totally suppressing RARα. In APL, RARA P2 methylation was unrelated to gender, age, presenting leukocyte counts and additional cytogenetic aberrations. For APL patients receiving all-trans retinoic acid for induction, P2 methylation did not affect the complete remission rates and survivals. RARA is the first myeloid-specific transcription factor shown to be dysregulated by both translocation and aberrant methylation. © 2005 Nature Publishing Group All rights reserved.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leuen_HK
dc.relation.ispartofLeukemiaen_HK
dc.subject.meshAcute Diseaseen_HK
dc.subject.meshBiological Transporten_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLeukemia, Myeloid - geneticsen_HK
dc.subject.meshLeukemia, Promyelocytic, Acute - etiology - geneticsen_HK
dc.subject.meshPolymerase Chain Reactionen_HK
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma - geneticsen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshReceptors, Retinoic Acid - geneticsen_HK
dc.subject.meshRecurrenceen_HK
dc.subject.meshRemission Inductionen_HK
dc.subject.meshSurvival Rateen_HK
dc.subject.meshTretinoin - therapeutic useen_HK
dc.titleAberrant promoter methylation of the retinoic acid receptor alpha gene in acute promyelocytic leukemiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0887-6924&volume=19&issue=12&spage=2241&epage=6&date=2005&atitle=Aberrant+promoter+methylation+of+the+retinoic+acid+receptor+alpha+gene+in+acute+promyelocytic+leukemiaen_HK
dc.identifier.emailChim, CS:jcschim@hku.hken_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.leu.2403937en_HK
dc.identifier.pmid16239915-
dc.identifier.scopuseid_2-s2.0-28544440377en_HK
dc.identifier.hkuros122073en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-28544440377&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2241en_HK
dc.identifier.epage2246en_HK
dc.identifier.isiWOS:000233462300027-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridWong, SY=7404590959en_HK
dc.identifier.scopusauthoridPang, A=7007044165en_HK
dc.identifier.scopusauthoridChu, P=7402159518en_HK
dc.identifier.scopusauthoridLau, JS=36903981300en_HK
dc.identifier.scopusauthoridWong, KF=7404759860en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.citeulike356369-

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