TrivalentAntimonialsInduceDegradationofthePML-RARaOncoproteinandReorganizationofthePromyelocyticLeukemiaNuclearBodiesinAcutePromyelocyticLeukemiaNB4CellsByStefanMu¨ller,WilsonH.Miller,Jr,andAnneDejeanAcutepromyelocyticleukemia(APL)ischaracterizedbyaantimonialsalsohavestrikingeffectsonRA-sensitiveandspecifict(15;17)chromosomaltranslocationthatfusestheRA-resistantAPLcells.TreatmentoftheAPL-derivedNB4genesencodingthepromyelocyticleukemiaprotein(PML)cellsandtheRA-resistantsubcloneNB4R4withantimonyandtheretinoicacidreceptora(RARa).Theresultingtrioxideorpotassiumantimonyltartrattriggersthedegrada-PML-RARaproteininducesablockinthedifferentiationoftionofthefusionproteinandtheconcomitantreorganiza-themyeloidprogenitorcells,whichcanbereleasedbytionofthePMLnuclearbodies.Inaddition,asreportedforretinoicacid(RA)invitroandinvivo.TheRA-inducedAs2O3,theantimonialsprovokeapoptosisofNB4andNB4R4differentiationofAPLblastsisparalleledbythedegradationcells.Themechanismofantimonyactionislikelytobeofthefusionproteinandtherelocationofwild-typePMLsimilartothatofAs2O3,notablybothsubstancesinducethefromaberrantnuclearstructurestoitsnormallocalizationinattachmentoftheubiquitin-likeSUMO-1moleculetothenuclearbodies.Recently,arsenictrioxide(As2O3)treatmentPMLmoietyofPML-RARa.Fromthesedata,weproposewasproposedasanalternativetherapyinAPL,becauseitthat,inanalogytoAs2O3,antimonialsmighthaveabenefi-caninducecompleteremissioninbothRA-sensitiveandcialtherapeuticeffectonAPLpatients,perhapswithless-resistantAPLpatients.Intriguingly,As2O3wasalsoshowntoxicitythanarsenic.toinducedegradationofthePML-RARachimeraandto௠1998byTheAmericanSocietyofHematology.reorganizePMLnuclearbodies.HereweshowthattrivalentCUTEPROMYELOCYTICleukemia(APL)representsthecombinationofRAwithchemotherapyhasimprovedtheAabout10%ofacutemyeloidleukemiacases.APLissurvivalofpatientswithAPL.15-17characterizedbyaspecificdifferentiationblockofthemyeloidThePML-RARachimeramayexertitsdominantnegativeprogenitorcellsatthepromyel