Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine英文文献资料.docVIP

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Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine英文文献资料.doc

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Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine英文文献资料

HindawiPublishingCorporation AdvancesinHematology Volume2012,ArticleID727683,12pages doi:10.1155/2012/727683 ResearchArticle BoneMarrowandPeripheralBloodAMLCellsAreHighly SensitivetoCNDAC,theActiveFormofSapacitabine SuchetaJagan,1,2,3LauraA.Paganessi,1,2,3RobinR.Frank,1,2,3ParameswaranVenugopal, 2,3 MelissaLarson,2,3andKentW.ChristophersonII1,2,3,4 1 SectionofBoneMarrowTransplantandCellTherapy,RushUniversityMedicalCenter,1725WestHarrisonStreet, Chicago,IL60612,USA 2 3 4 RushUniversityCancerCenter,1725WestHarrisonStreet,Chicago,IL60612,USA SectionofHematology,RushUniversityMedicalCenter,1725WestHarrisonStreet,Chicago,IL60612,USA DepartmentofAnatomyandCellBiology,RushUniversityMedicalCenter,1725WestHarrisonStreet,Chicago,IL60612,USA CorrespondenceshouldbeaddressedtoKentW.ChristophersonII,kent christopherson@ Received18June2012;Accepted4August2012 AcademicEditor:SeijiFukuda Copyright?2012SuchetaJaganetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Achievingimprovementsinsurvivalandreducingrelapseremainsachallengeinacutemyelogenousleukemia(AML)patients.This studyevaluatedtheinvitroe?cacyoftheactiveformofnovelagentsapacitabine,CNDAC,comparedtocurrentchemotherapeutic drugsAra-CandmitoxantroneusingtwoAMLcelllines,HL-60(promyelocytic)andTHP-1(monocytic),aswellasbonemarrow (BM)andperipheralblood(PB)cellscollectedfromAMLpatients.Celllineswereexposedtocompoundfor3–6daysandprimary cellsfor4days.Theviabilityofprimarycellswasadditionallyevaluated3,7,and31daysafterremovaloftestedcompoundto determinethedurabilityoftheresponse.OurstudiesindicatethatCNDACandmitoxantronehaveagreaterimpactonviability thanara-CinprimaryAMLcellsandAMLcelllines.CNDACismoree?ectiveatreducingviabilityandinducingapoptosisthan ara-CatequivalentconcentrationsintheTHP-1cellline,whichisde?nedasdisplayingresistancetoara-C.Assapacitabinehas showninvivoactivityatclinica