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1、白血病靶向治疗娄世锋HematopoieticStemCellWhatIsaHematopoieticStemCell?Ahematopoieticstemcellisacellisolatedfromthebloodorbonemarrowthatcanrenewitself,candifferentiatetoavarietyofspecializedcells,canmobilizeoutofthebonemarrowintocirculatingblood,andcanundergoprogrammedcelldeath,calledapoptos
2、is—aprocessbywhichcellsthataredetrimentalorunneededself-destruct.造血干细胞造血干细胞stemcellThisstemcellfuelschronicmyelogenousleukemia,atypeofcancer.造血干细胞CD150+(red)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
3、Leukemia:aviewinpastLeukemicstemcellOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationGriffinJDetal,Blood(1986)68:1185LeukemicstemcellAML-CFUinvitroSL-ICinvivoproliferationinSCIDself-renewalfirstevidenceofLSCLeukemicstemcellPropertiesofLSCCellsurfacemarkersAML:CD34+,CD
4、38–,CD71–,HLA–DR–,CD90–,CD117–,andCD123+GuzmanML,JordanCT.Considerationsfortargetingmalignantstemcellsinleukemia.CancerControl.2004;11:97–104CML:CD34+,CD38–HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Elucidatingcriticalmechanismsofderegulatedstemcellturnoverinthechronicphaseofchr
5、onicmyeloidleukemia.Leukemia.2002;16:549–558.PropertiesofLSCself-renewalBonnetD,DickJE.Humanacutemyeloidleukemiaisorganizedasahierarchythatoriginatesfromaprimitivehematopoieticcell.NatMed.1997;3:730–737.CellcyclestatusAMLandCMLstemcellsmaintainpopulationsthatarequiescentGuanY,Gerh
6、ardB,HoggeDE.Detection,isolation,andstimulationofquiescentprimitiveleukemicprogenitorcellsfrompatientswithacutemyeloidleukemia(AML)PropertiesofLSCUniquemolecularfeaturesAMLcellsupregulatethegenesencodingIRF-1andDAPkinaseGuzmanML,UpchurchD,GrimesB,etal.Blood.2001;97:2177–2179Highco
7、nstitutivelevelsofNF-BactivityGuzmanML,NeeringSJ,UpchurchD,etal.Blood.2001;98:2301–2307CMLcellsarecapableofautocrineinterleukin(IL)-3growthstimulationandactivationofSTAT5.[HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Leukemia.2002;16:549–558OriginofLSCandMolecularPathogenesishemat
8、opoieticstemcell(HSC)othertypesof
