白血病干细胞研究课件

白血病靶向治疗娄世锋白血病干细胞研究HematopoieticStemCellWhatIsaHematopoieticStemCell?Ahematopoieticstemcellisacellisolatedfromthebloodorbonemarrowthatcanrenewitself,candifferentiatetoavarietyofspecializedcells,canmobilizeoutofthebonemarrowintocirculatingblood,andcanundergoprogrammedcelldeath,calledapoptosis—aprocessbywhichcellsthataredetrimentalorunneededself-destruct.白血病干细胞研究造血干细胞白血病干细胞研究造血干细胞白血病干细胞研究stemcellThisstemcellfuelschronicmyelogenousleukemia,atypeofcancer.白血病干细胞研究造血干细胞CD150+(red)白血病干细胞研究Stemcell:CellMarkers

人类造血干细胞特征细胞表面标志

阳性标志CD34+CD133+

弱阳性标志Thy-1(CDw90),c-kit

阴性标志CD38,CD33,T/B细胞标志，CD71,DR染色排斥Rh123,Hoechst33342白血病干细胞研究白血病干细胞研究白血病干细胞研究Leukemia:aviewinpast白血病干细胞研究LeukemicstemcellOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationGriffinJDetal,Blood(1986)68:1185白血病干细胞研究LeukemicstemcellAML-CFUinvitroSL-ICinvivoproliferationinSCIDself-renewal

firstevidenceofLSC白血病干细胞研究Leukemicstemcell白血病干细胞研究PropertiesofLSCCellsurfacemarkers

AML:CD34+,CD38–,CD71–,HLA–DR–,CD90–,CD117–,andCD123+GuzmanML,JordanCT.Considerationsfortargetingmalignantstemcellsinleukemia.CancerControl.2004;11:97–104

CML:

CD34+,CD38–HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Elucidatingcriticalmechanismsofderegulatedstemcellturnoverinthechronicphaseofchronicmyeloidleukemia.Leukemia.2002;16:549–558.白血病干细胞研究PropertiesofLSCself-renewalBonnetD,DickJE.Humanacutemyeloidleukemiaisorganizedasahierarchythatoriginatesfromaprimitivehematopoieticcell.NatMed.1997;3:730–737.Cellcyclestatus

AMLandCMLstemcellsmaintainpopulationsthatarequiescent

GuanY,GerhardB,HoggeDE.Detection,isolation,andstimulationofquiescentprimitiveleukemicprogenitorcellsfrompatientswithacutemyeloidleukemia(AML)

白血病干细胞研究PropertiesofLSCUniquemolecularfeatures

AMLcellsupregulatethegenesencodingIRF-1andDAPkinaseGuzmanML,UpchurchD,GrimesB,etal.Blood.2001;97:2177–2179

HighconstitutivelevelsofNF-BactivityGuzmanML,NeeringSJ,UpchurchD,etal.Blood.2001;98:2301–2307CMLcellsarecapableofautocrineinterleukin(IL)-3growthstimulationandactivationofSTAT5

.[HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Leukemia.2002;16:549–558白血病干细胞研究OriginofLSCandMolecularPathogenesis

hematopoieticstemcell(HSC)othertypesofearlystemorprogenitorcells

白血病干细胞研究OriginofLSCandMolecularPathogenesisCozzioA,PassegueE,AytonPM,KarsunkyH,ClearyML,WeissmanIL.GenesDev.2003;17:3029–3035白血病干细胞研究CurrentTherapiesandFutureDirectionsOurincreasingunderstandingofLSChasallowedareassessmentofourclinicalapproachtoAMLandCML.白血病干细胞研究CurrentTherapiesandFutureDirections白血病干细胞研究白血病干细胞研究CurrentTherapiesandFutureDirectionsTargetingLSCsurfacemolecules

CD33targetedapproachIL-3fusiontodiphtheriatoxinIL-3fusiontoPE白血病干细胞研究CurrentTherapiesandFutureDirectionsPEIL-3白血病干细胞研究CurrentTherapiesandFutureDirectionsInducingLSC-specificimmunity

TcellclonesspecifictominorhistocompatibilityantigensonLSC.

BonnetD,WarrenEH,GreenbergPD,DickJE,RiddellSR.CD8(+)minorhistocompatibilityantigen-specificcytotoxicTlymphocytecloneseliminatehumanacutemyeloidleukemiastemcells.ProcNatlAcadSciUSA.1999;96:8639–8644.白血病干细胞研究CurrentTherapiesandFutureDirectionsTargetingLSC-specificmolecularpathways

inhibitorsoftheFlt3transmembranetyrosinekinaseProteasomeinhibitordrugs

inhibitNF-kB,normalHSCarerelativelyresistanttoproteasomeinhibitioninhibitsignalinginthePI3kinase(PI3K)pathway白血病干细胞研究生物治疗CIKCell白血病干细胞研究生物治疗CIKCell白血病干细胞研究白血病干细胞研究白血病干细胞研究生物治疗DendriticCells

白血病干细胞研究白血病干细胞研究白血病干细胞研究DC—CIK细胞治疗自体外周血造血干细胞

移植后急性髓性白血病的临床研究陈智超4例患者已分别无病生存2年半、2年、2年、1年。临床内科杂志2007年9月第24卷第9期2007，Vol，24，No．白血病干细胞研究自体CIK细胞辅助治疗非霍奇金淋巴瘤患者的临床观察

对6例非霍奇金淋巴瘤并且存在结外器官侵犯的患者，CIK细胞输注后可见患者体内CD3CD56细胞较前增加，影像学复查显示肿块缩小，治疗过程中主要出现畏寒、发热，未观察到其他明显副作用苏州大学附属第二医院血液科中国血液流变学杂志．2007；17(1)白血病干细胞研究化疗联合自体细胞因子诱导杀伤细胞

治疗急性白血病的临床观察

江浩刘开彦童春容江滨陆道培白血病干细胞研究白血病干细胞研究CurrentTherapiesandFutureDirectionsSpecificmethodsfortargetingtheCMLstemcellmayalsorelatetoPI3K/AktandNF-Bsignalingpathways,bothofwhichareknowntobeactiveinCMLcells.However,notallpathwaysrelevanttothesurvivalofleukemiccellsarenecessaryforsurvivalofLSC.白血病干细胞研究SummaryAbetterunderstandingofhumanLSCislikelytoprovideexcitingopportunitiestodevelopimprovedleukemiatherapies.SuchapproachescanbetailoredtotheuniquebiologicalpropertiesoftheLSC,whileprotectingthecriticalfunctionsofnormalHSC.Asoutlinedabove,severaldifferentapproachesareemergingthatshowpromiseasmorespecificmeanstotargettheLSCpopulation.Inaddition,powerfulanimalmodelsystemshaverecentlybeendescribedthatwillpermitdetailedanalysisofLSCandthemolecularmechanismsthatcontroltheirgrowthandsurvival.21Suchmodelsalsoofferexcellentsystemsinwhichnovelexperimentaltherapiescanbeevaluated.Forthefuture,criticalquestionsrequirefur