TitleTargetingHDAC3,anewpartnerproteinofAKTinthereversalofchemoresistanceinacutemyeloidleukemiaviaDNAdamageresponseAbstractResistancetocytotoxicchemotherapydrugsremainsasthemajorcauseoftreatmentfailureinacutemyeloidleukemia.Histonedeacetylases(HDAC)areimportantregulatorstomaintainchromatinstructureandcontrolDNAdamage;nevertheless,howeachHDACregulatesgenomestabilityremainsunclear,especiallyundergenomestressconditions.Here,weidentifiedamechanismbywhichHDAC3regulatesDNAdamagerepairandmediatesresistancetochemotherapydrugs.InadditiontoinducingDNAdamage,chemotherapydrugstriggerupregulationofHDAC3expressioninleukemiacells.Usinggeneticandpharmacologicalapproaches,weshowthatHDAC3contributestochemotherapyresistancebyregulatingtheactivationofAKT,awell-documentedfactorindrugresistancedevelopment.HDAC3bindstoAKTanddeacetylatesitatthesiteLys20,therebypromotingthephosphorylationofAKT.ChemotherapydrugexposureenhancestheinteractionbetweenHDAC3andAKT,resultingindecreaseinAKTacetylationandincreaseinAKTphosphorylation.WhereasHDAC3depletionorinhibitionabrogatestheseresponsesandmeanwhilesensitizesleukemiacellstochemotoxicity-inducedapoptosis.Importantly,invivoHDAC3suppressionreducesleukemiaprogressionandsensitizesMLL-AF9+leukemiatochemotherapy.Ourfindingssuggestthat白殿疯病是什么样的白癜风患者的饮食
