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

人類造血干細(xì)胞特征細(xì)胞表面標(biāo)志

陽性標(biāo)志CD34+CD133+

弱陽性標(biāo)志Thy-1(CDw90),c-kit

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

firstevidenceofLSC白血病干細(xì)胞研究Leukemicstemcell白血病干細(xì)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(xì)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(xì)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(xì)胞研究OriginofLSCandMolecularPathogenesis

hematopoieticstemcell(HSC)othertypesofearlystemorprogenitorcells

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

CD33targetedapproachIL-3fusiontodiphtheriatoxinIL-3fusiontoPE白血病干細(xì)胞研究CurrentTherapiesandFutureDirectionsPEIL-3白血病干細(xì)胞研究CurrentTherapiesandFutureDirectionsInducingLSC-specificimmunity

TcellclonesspecifictominorhistocompatibilityantigensonLSC.

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

inhibitorsoftheFlt3transmembranetyrosinekinaseProteasomeinhibitordrugs

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

白血病干細(xì)胞研究白血病干細(xì)胞研究白血病干細(xì)胞研究DC—CIK細(xì)胞治療自體外周血造血干細(xì)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(nèi)科雜志2007年9月第24卷第9期2007，Vol，24，No．白血病干細(xì)胞研究自體CIK細(xì)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(jié)外器官侵犯的患者，CIK細(xì)胞輸注后可見患者體內(nèi)CD3CD56細(xì)胞較前增加，影像學(xué)復(fù)查顯示腫塊縮小，治療過程中主要出現(xiàn)畏寒、發(fā)熱，未觀察到其他明顯副作用蘇州大學(xué)附屬第二醫(yī)院血液科中國血液流變學(xué)雜志．2007；17(1)白血病干細(xì)胞研究化療聯(lián)合自體細(xì)胞因子誘導(dǎo)殺傷細(xì)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(xì)胞研究白血病干細(xì)胞研究CurrentTherapiesandFutureDirectionsSpecificmethodsfortargetingtheCMLstemcellmayalsorelatetoPI3K/AktandNF-Bsignalingpathways,bothofwhichareknowntobeactiveinCMLcells.However,notallpathwaysrelevanttothesurvivalofleukemiccellsarenecessaryforsurvivalofLSC.白血病干細(xì)胞研究SummaryAbetterunderstandingofhumanLSCislikelytoprovideexcitingopportunitiestodevelopimprovedleukemiatherapies.SuchapproachescanbetailoredtotheuniquebiologicalpropertiesoftheLSC,whileprotectingthecriticalfunctionsofnormalHSC.Asoutlinedabove,severaldifferentapproachesareemergingthatshowpromiseasmorespecificmeanstotargettheLSCpopulation.Inaddition,powerfulanimalmodelsystemshaverecentlybeendescribedthatwillpermitdetailedanalysisofLSCandthemolecularmechanismsthatcontroltheirgrowthandsurvival.21Suchmodelsalsoofferexcellentsystemsinwhichnovelexperimentaltherapiescanbeevaluated.Forthefuture,criticalquestionsrequirefur