Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator 英文参考文献.docVIP

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Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator 英文参考文献.doc

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Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator 英文参考文献

RetroviralIntegrationMutagenesisinMiceand ComparativeAnalysisinHumanAMLIdentifyReduced PTP4A3ExpressionasaPrognosticIndicator Rene′eBeekman1,MarijkeValkhof1,StefanJ.Erkeland1,ErdoganTaskesen1,VeronikaRockova1,2, JustineK.Peeters1,PeterJ.M.Valk1,BobLo¨wenberg1,IvoP.Touw1* 1Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands, 2Department of Biostatistics, Erasmus University Medical Center, Rotterdam,TheNetherlands Abstract Acutemyeloidleukemia(AML)resultsfrommultiplegeneticandepigeneticaberrations,manyofwhichremainunidentified. Frequent loss of large chromosomal regions marks haplo-insufficiency as one of the major mechanisms contributing to leukemogenesis.However, whichhaplo-insufficient genes(HIGs)areinvolvedinleukemogenesisis largelyunknownand powerfulexperimentalstrategiesaimedattheiridentification arecurrentlylacking.Here,wepresentanewapproachto discoverHIGs,usingretroviralintegrationmutagenesisinmiceinwhichmethylatedviralintegrationsitesandneighbouring geneswereidentified.Intotalwemapped6geneswhichareflankedbymethylatedviralintegrationsites(mVIS).Threeof these,i.e.,Lrmp,Hcls1andPrkrir,wereupregulatedandone,i.e.,Ptp4a3,wasdownregulatedintheaffectedtumor.Next, weinvestigatedtheroleofPTP4A3inhumanAMLandweshowthatPTP4A3expressionisanegativeprognosticindicator, independentofotherprognosticparameters.Inconclusion,ournovelstrategyhasidentifiedPTP4A3topotentiallyhavea roleinAML,ononehandasacandidateHIGcontributingtoleukemogenesisinmiceandontheotherhandasaprognostic indicatorinhumanAML. Citation:BeekmanR,ValkhofM,ErkelandSJ,TaskesenE,RockovaV,etal.(2011)RetroviralIntegrationMutagenesisinMiceandComparativeAnalysisinHuman AMLIdentifyReducedPTP4A3ExpressionasaPrognosticIndicator.PLoSONE6(10):e26537.doi:10.1371/journal.pone.0026537 Editor:ChristianScho¨nbach,KyushuInstituteofTechnology,Japan ReceivedFebruary4,2011;AcceptedSeptember28,2011;PublishedOctober20,2011 Copyright: ? 2011 Beekman et al. This is an open-access article distri