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1、白血病靶向治疗娄世锋HematopoieticStemCellWhatIsaHematopoieticStemCell?Ahematopoieticstemcellisacellisolatedfromthebloodorbonemarrowthatcanrenewitself,candifferentiatetoavarietyofspecializedcells,canmobilizeoutofthebonemarrowintocirculatingblood,andcanundergoprogrammedcelldeath,calledapoptosis—ap
2、rocessbywhichcellsthataredetrimentalorunneededself-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,Hoechst33342Leukemia:a
3、viewinpastLeukemicstemcellOnlyasmallsubsetofcancercellsiscapableofextensiveproliferationGriffinJDetal,Blood(1986)68:1185LeukemicstemcellAML-CFUinvitroSL-ICinvivoproliferationinSCIDself-renewalfirstevidenceofLSCLeukemicstemcellPropertiesofLSCCellsurfacemarkersAML:CD34+,CD38–,CD71–,HLA–D
4、R–,CD90–,CD117–,andCD123+GuzmanML,JordanCT.Considerationsfortargetingmalignantstemcellsinleukemia.CancerControl.2004;11:97–104CML:CD34+,CD38–HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Elucidatingcriticalmechanismsofderegulatedstemcellturnoverinthechronicphaseofchronicmyeloidleukemia.
5、Leukemia.2002;16:549–558.PropertiesofLSCself-renewalBonnetD,DickJE.Humanacutemyeloidleukemiaisorganizedasahierarchythatoriginatesfromaprimitivehematopoieticcell.NatMed.1997;3:730–737.CellcyclestatusAMLandCMLstemcellsmaintainpopulationsthatarequiescentGuanY,GerhardB,HoggeDE.Detection,is
6、olation,andstimulationofquiescentprimitiveleukemicprogenitorcellsfrompatientswithacutemyeloidleukemia(AML)PropertiesofLSCUniquemolecularfeaturesAMLcellsupregulatethegenesencodingIRF-1andDAPkinaseGuzmanML,UpchurchD,GrimesB,etal.Blood.2001;97:2177–2179HighconstitutivelevelsofNF-Bactivity
7、GuzmanML,NeeringSJ,UpchurchD,etal.Blood.2001;98:2301–2307CMLcellsarecapableofautocrineinterleukin(IL)-3growthstimulationandactivationofSTAT5.[HolyoakeTL,JiangX,DrummondMW,EavesAC,EavesCJ.Leukemia.2002;16:549–558OriginofLSCandMolecularPathogenesishematopoieticstemcell(HSC)othertypesof
