Mutation Patterns of 16 Genes in Primary and Secondary Acute Myeloid Leukemia (AML) with Normal Cytogenetics 英文参考文献.docVIP

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Mutation Patterns of 16 Genes in Primary and Secondary Acute Myeloid Leukemia (AML) with Normal Cytogenetics 英文参考文献.doc

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Mutation Patterns of 16 Genes in Primary and Secondary Acute Myeloid Leukemia (AML) with Normal Cytogenetics 英文参考文献

MutationPatternsof16GenesinPrimaryandSecondary AcuteMyeloidLeukemia(AML)withNormal Cytogenetics MartaFernandez-Mercado1,BonHamYip1,AndreaPellagatti1,CarwynDavies1,Mar?′aJose′ Larrayoz2, ToshinoriKondo3,CristinaPe′rez4,SallyKillick5,Emma-JaneMcDonald5,Mar?′aDoloresOdero2,6, XabierAgirre7,FelipePro′sper7,Mar?′aJose′ Calasanz2,JamesS.Wainscoat1,JacquelineBoultwood1* 1LLRMolecularHaematologyUnit,NDCLS,JohnRadcliffeHospital,Oxford,UnitedKingdom,2DepartmentofGenetics,UniversityofNavarra,Pamplona,Spain,3Division of Hematology, Kawasaki Medical School, Okayama, Japan, 4Laboratory of Myeloproliferative Syndromes, Oncology Area, Foundation for Applied Medical Research, Cl?′nicaUniversitaria,UniversidaddeNavarra,Pamplona,Spain,5DepartmentofHaematology,RoyalBournemouthHospital,Bournemouth,UnitedKingdom,6Divisionof Oncology, Center for Applied Medical Research, Universidad de Navarra, Pamplona, Spain, 7Division of Cancer and Area of Cell Therapy and Hematology Service, FoundationforAppliedMedicalResearch,Cl?′nicaUniversitaria,UniversidaddeNavarra,Pamplona,Spain Abstract Acutemyeloidleukemiapatientswithnormalcytogenetics(CN-AML)accountforalmosthalfofAMLcases.Weaimedto studythefrequencyandrelationshipofawiderangeofgenespreviouslyreportedasmutatedinAML(ASXL1,NPM1,FLT3, TET2,IDH1/2,RUNX1,DNMT3A,NRAS,JAK2,WT1,CBL,SF3B1,TP53,KRASandMPL)inaseriesof84CN-AMLcases.Themost frequentlymutatedgenesinprimarycaseswereNPM1(60.8%)andFLT3(50.0%),andinsecondarycasesASXL1(48.5%)and TET2(30.3%).Weshowedthat85%ofCN-AMLpatientshavemutationsinatleastoneofASXL1,NPM1,FLT3,TET2,IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations;seventeencasespresentedmutationsofatleastoneofthesegenes.However,therewasnoconsistentpatternin mutationacquisitionduringdiseaseprogression.Thisreportconcernstheanalysisofthelargestnumberofgenemutations inCN-AMLstudiedtodate,andprovidesinsightintothemutationalprofileofCN-AML. Citation:Fernandez-Me