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组蛋白乙酰转移酶MOF对急性髓系白血病的影响及其作用机制研究.docx

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组蛋白乙酰转移酶MOF对急性髓系白血病的影响及其作用机制研究 Title:TheRoleandMechanismsofHistoneAcetyltransferaseMOFinAcuteMyeloidLeukemia Introduction: Acutemyeloidleukemia(AML)isatypeofhematologicmalignancycharacterizedbytheaccumulationofimmaturemyeloidcellsinthebonemarrowandblood.Despiteadvancesintreatment,theprognosisforAMLremainspoor.Therefore,understandingthemolecularmechanismsunderlyingAMLdevelopmentandprogressioniscrucialfordevelopingnoveltherapeuticstrategies.ThisstudyaimedtoinvestigatetheimpactofthehistoneacetyltransferaseMOF(maleabsentonthefirst)onAMLandelucidateitsunderlyingmechanisms. HistoneacetyltransferaseMOF: MOFisakeymemberoftheMYSTfamilyofhistoneacetyltransferases.ItplaysanessentialroleinacetylatinghistoneH4atlysine16(H4K16ac),catalyzingtheadditionofacetylgroupstothelysineresidueofhistoneproteins.Thishistonemodificationisassociatedwithtranscriptionalactivationandchromatinremodeling.TheaberrantexpressionordysfunctionofMOFhasbeenimplicatedinnumerouscancertypes,includingAML. ImpactofMOFonAML: StudieshaverevealedthatMOFexpressionisupregulatedinAMLpatientscomparedtohealthyindividuals.ElevatedMOFexpressioniscorrelatedwithpoorerprognosisandincreaseddrugresistanceinAMLpatients.ExperimentalstudiesutilizingMOFknockdownorknockoutmodelshaveshownthatreducingoreliminatingMOFexpressionresultsinimpairedleukemogenesisandincreasedsensitivitytochemotherapeuticagents,suggestingthatMOFplaysacriticalroleinAMLdevelopmentanddrugresistance. MOFandchromatinremodeling: MOF-mediatedacetylationofhistoneH4atlysine16promotesanopenchromatinstructure,allowingforincreasedaccessibilityoftranscriptionfactorsandotherregulatoryproteinstotheirtargetgenes.Thisenhancesgeneexpressionandfacilitatesleukemiccellproliferationandsurvival.Additionally,MOFhasbeenshowntointeractwithotherchromatinremodelingcomplexes,suchasthemixed-lineageleukemia(MLL)complex,andfacilitatetherecruitmentofthesecomplexestospecificgeneloci,resultingingeneactivationandleukemogenesis. MOFandtranscriptionalregulation: Beyonditsdirectimpactonchromatin