急性髓系白血病干细胞nod2fscid小鼠白血病模型的建立

急性髓系白血病干细胞nod2fscid小鼠白血病模型的建立

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大小:7.82 MB

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时间:2019-03-02

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1、硕士学位论文EstablishmentofanAnimalmodelofHumanmyeloidleukemiainNOD/SCIDMiceUsingacutemyeloidLeukemiastemcellsName:LirongweiSupervisor:XuBinglngAbstractBackgroundAcmemyeloidleukemia(AML)isakindoflethaldiseaseoriginatingfromacutemyeloidleukemiastemcellswiththecharacteristicsofincontrolla

2、bleproliferationofmyeloidcells.TheclinicalomcomeofAMLisrelatedwithalotoffactorssuchasmyeloidcelltype,cytogeneticchangeaswellasthebiologicalcharacteristicsofclones.AlthoughtreatmentofAMLisdevelopingreallyfastrecentyearswithabettertreatmentefficacybeingachieved,relapseandtreatmentre

3、latedsideeffectstillremaintobcthemainobstacleoftheimprovementofefficacyofAMLtreatment.PreviousstudieshavedemonstratedthatchemotherapyCan’teliminateleukemiastemcellsandthusremainingleukemiastemcellsCancausetherelapseofpatients.Sonowresearchersarefocusingonthepathogenesisofleukemias

4、temcellstodevelopnewdrugsfortreatingAML.AMLoriginatesfromasmallnumberofcellsnamedAMLstemcells(LSCs)whicharecharacterizedbytheirabilitytoself-renew,unlimitedrepopulatingpotentialandlongresidenceinaquiescentstateofG0/G1phase.AMLstemcellshavesomecommonmarkerssuchasCD34十andCD38。.Theya

5、remoreresistanttocommonchemo·drugsandhavecross-resistance晰t11alotofdrugs.Therefore,methodtoeliminateAMLstemcellshavebecomethehotpointforleukemiaresearches.AlthoughAMLhasmanytypes,allothertypesofAMLleukemiastemcells,apartfromAPL,sharethesamesurfacemarkerssuchasCD34+andCD38。.Previou

6、sstudiesfocusingLSCsalwaysselectCD34+andCD38。cellsfromthebonemarrowofpatientsastheirexperimentalsubjects.However,theresourceisnotenoughforresearch.Thus,itrequiresanewresourcetoselectLSCs.KGlacelllineoriginatesfromamalepatientwhohadAML-M0andWasresistanttochemo-drugs.Thiscelllinehas

7、higherexpressionsofMDRandP-glycoprotcinandishighlyresistanttochemo-drugs.PreviousstudieshavealreadyselectLSCsfromKGlacellstodoresearchesfocusingonLSCs.ThefoundationforresearchesfocusingonthedrugstoeliminateLSCsistheestablishmentofanimalmodelsofLSCs.Luckily,oneofthecharacteristicso

8、fLSCsistheabilitytoestablishleuke

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