DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia 英文参考文献.docVIP

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DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia 英文参考文献.doc

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DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia 英文参考文献

DNAMethylationProfilesandTheirRelationshipwith CytogeneticStatusinAdultAcuteMyeloidLeukemia SaraAlvarez1*,JavierSuela1,AnaValencia2,Agust?′nFerna′ndez3,MarkWunderlich4,XabierAgirre5, FelipePro′sper5,Jose′ IgnacioMart?′n-Subero3,8,AlbaMaiques1,FrancescoAcquadro1,SandraRodriguez Perales1,Mar?′aJose′ Calasanz6,JoseRoman-Go′mez7,ReinerSiebert8,JamesC.Mulloy4,Jose′ Cervera2, MiguelAngelSanz2,ManelEsteller3,JuanC.Cigudosa1* 1Molecular Cytogenetics Group, Centro Nacional Investigaciones Oncologicas (CNIO), Centro de Investigaciones de Enfermedades Raras (CIBERER), Madrid, Spain, 2HematologyService,HospitalUniversitarioLaFe,Valencia,Spain,3CancerEpigeneticsandBiologyProgram,BellvitgeInstituteforBiomedicalResearch-CatalanInstitute of Oncology(IDIBELL-ICO), Barcelona, Spain, 4Division of Experimental Hematology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine,Cincinnati,Ohio,UnitedStatesofAmerica,5DivisionofCancerandAreaofCellTherapyandHematologyService,FoundationforAppliedMedicalResearch, Cl?′nica Universitaria, Universidad de Navarra, Pamplona, Spain, 6Department of Genetics, University of Navarra, Pamplona, Spain, 7Hematology Service, Hospital UniversitarioReinaSofia,Co′rdoba,Spain,8InstituteofHumanGenetics,UniversityHospitalSchleswig-Holstein,CampusKiel,Christian-AlbrechtsUniversity,Kiel,Germany Abstract Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology.However,furtherstudiestodiscusstheprognosticvalueandtherelationshipoftheepigeneticsignatures withdefinedgenomicrearrangementsinacutemyeloidleukemiaarerequired. Methodology/PrincipalFindings:Wecarriedouthigh-throughputmethylationprofilingon116denovoAMLcasesandwe validatedthesignificantbiomarkersinanindependentcohortof244AMLcases.Methylationsignatureswereassociated withthepresenceofaspecificcytogeneticstatus.Innormalkaryotypecases,aberrantmethylationofthepromoterofDBC1 wasvalidatedasapredictorofthedis