白血病靶向治療婁世鋒白血病干細胞研究HematopoieticStemCellWhatIsaHematopoieticStemCell?Ahematopoieticstemcellisacellisolatedfromthebloodorbonemarrowthatcanrenewitself,candifferentiatetoavarietyofspecializedcells,canmobilizeoutofthebonemarrowintocirculatingblood,andcanundergoprogrammedcelldeath,calledapoptosis—aprocessbywhichcellsthataredetrimentalorunneededself-destruct.白血病干細胞研究造血干細胞白血病干細胞研究造血干細胞白血病干細胞研究stemcellThisstemcellfuelschronicmyelogenousleukemia,atypeofcancer.白血病干細胞研究造血干細胞CD150+(red)白血病干細胞研究Stemcell:CellMarkers

人類造血干細胞特征細胞表面標志

陽性標志CD34+CD133+

弱陽性標志Thy-1(CDw90),c-kit

陰性標志CD38,CD33,T/B細胞標志，CD71,DR染色排斥Rh123,Hoechst33342白血病干細胞研究白血病干細胞研究白血病干細胞研究Leukemia:aviewinpast白血病干細胞研究LeukemicstemcellOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationGriffinJDetal,Blood(1986)68:1185白血病干細胞研究LeukemicstemcellAML-CFUinvitroSL-ICinvivoproliferationinSCIDself-renewal

firstevidenceofLSC白血病干細胞研究Leukemicstemcell白血病干細胞研究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.白血病干細胞研究PropertiesofLSCself-renewalBonnetD,DickJE.Humanacutemyeloidleukemiaisorganizedasahierarchythatoriginatesfromaprimitivehematopoieticcell.NatMed.1997;3:730–737.Cellcyclestatus

AMLandCMLstemcellsmaintainpopulationsthatarequiescent

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

白血病干細胞研究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白血病干細胞研究OriginofLSCandMolecularPathogenesis

hematopoieticstemcell(HSC)othertypesofearlystemorprogenitorcells

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

CD33targetedapproachIL-3fusiontodiphtheriatoxinIL-3fusiontoPE白血病干細胞研究CurrentTherapiesandFutureDirectionsPEIL-3白血病干細胞研究CurrentTherapiesandFutureDirectionsInducingLSC-specificimmunity

TcellclonesspecifictominorhistocompatibilityantigensonLSC.

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

inhibitorsoftheFlt3transmembranetyrosinekinaseProteasomeinhibitordrugs

inhibitNF-kB,normalHSCarerelativelyresistanttoproteasomeinhibitioninhibitsignalinginthePI3kinase(PI3K)pathway白血病干細胞研究生物治療CIKCell白血病干細胞研究生物治療CIKCell白血病干細胞研究白血病干細胞研究白血病干細胞研究生物治療DendriticCells

白血病干細胞研究白血病干細胞研究白血病干細胞研究DC—CIK細胞治療自體外周血造血干細胞

移植后急性髓性白血病的臨床研究陳智超4例患者已分別無病生存2年半、2年、2年、1年。臨床內科雜志2007年9月第24卷第9期2007，Vol，24，No．白血病干細胞研究自體CIK細胞輔助治療非霍奇金淋巴瘤患者的臨床觀察

對6例非霍奇金淋巴瘤并且存在結外器官侵犯的患者，CIK細胞輸注后可見患者體內CD3CD56細胞較前增加，影像學復查顯示腫塊縮小，治療過程中主要出現畏寒、發熱，未觀察到其他明顯副作用蘇州大學附屬第二醫院血液科中國血液流變學雜志．2007；17(1)白血病干細胞研究化療聯合自體細胞因子誘導殺傷細胞

治療急性白血病的臨床觀察

江浩劉開彥童春容江濱陸道培白血病干細胞研究白血病干細胞研究CurrentTherapiesandFutureDirectionsSpecificmethodsfortargetingtheCMLstemcellmayalsorelatetoPI3K/AktandNF-Bsignalingpathways,bothofwhichareknowntobeactiveinCMLcells.However,notallpathwaysrelevanttothesurvivalofleukemiccellsarenecessaryforsurvivalofLSC.白血病干細胞研究SummaryAbetterunderstandingofhumanLSCislikelytoprovideexcitingopportunitiestodevelopimprovedleukemiatherapies.SuchapproachescanbetailoredtotheuniquebiologicalpropertiesoftheLSC,whileprotectingthecriticalfunctionsofnormalHSC.Asoutlinedabove,severaldifferentapproachesareemergingthatshowpromiseasmorespecificmeanstotargettheLSCpopulation.Inaddition,powerfulanimalmodelsystemshaverecentlybeendescribedthatwillpermitdetailedanalysisofLSCandthemolecularmechanismsthatcontroltheirgrowthandsurvival.21Suchmodelsalsoofferexcellentsystemsinwhichnovelexperimentaltherapiescanbeevaluated.Forthefuture,criticalquestionsrequirefur