《骨髓增殖性腫瘤》PPT課件

《骨髓增殖性腫瘤》PPT課件

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時(shí)間:2019-06-27

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1、HongzhiXuShandongProvincialHospitalMyeloproliferativeDisordersCONTENTSPathogenesisandmanagementofessentialthrombocythemiaIdiopathicerythrocytosis:adisappearingentityTherapeuticpotentialofJAK2inhibitorsPathogenesisandmanagementofessentialthrombocythemiaPathogenesisRelations

2、hipofETtoPVandPMFThelevelofJAK2-STAT5signalingprovidesarheostatthatdetermineswhetherthediseasephenotypeispredominantlyerythroidormegakaryocytic.Severallinesofevidencesuggestablurringofthedistinctionbetweenthesedisorders.AproporationofpatientsdiagnosedwithET(seeTable1forcri

3、teria)harborincreasedlevelsofbonemarrowreticulinintheabsenceofotherfeaturessuggestingadiagnosisofPMFThevariabledegreeofreticulinaccumulationreflectsthecombinedeffectsofgeneticbackground,diseaseduration,therapy,clonalburdenandtheacquisitionofadditionalgeneticlesions.Table1.

4、Suggesteddiagnosticcriteriaforessentialthrombocythemia(ET)DiagnosisrequiresA1-A3ORA1+A3-A5A1Sustainedplateletcount>450X109/L.A2Presenceofanacquiredpathogeneticmutation(eg,inJAK2orMPL).A3Noothermyeloidmalignancy,especiallypolycythemiavera(PV),primarymyelofibrosis(PMF),chron

5、icmyeloidleukemia(CML)ormyelodysplasticsyndrome(MDS).A4Noreactivecauseforthrombocytosisandnormalironstores.A5Bonemarrowtrephinehistologyshowingincreasedmegakaryocyteswithprominentlargehyperlobatedforms;reticulinisgenerallynotincreased(≤2ona0-4scale).FamilialPredispositiont

6、oETandOtherMyeloproliferativeNeoplasmsArelativeriskof7.4fordevelopingETinthosewithanaffectedfirst-degreerelative.AreMutationsinJAK2Disease-initiatingEvents?TheacquisitionofaJAK2mutationwasprecededbyeitheradeletionofchromosome20q24oramutationinTET2.Directevidencenowexistsde

7、monstratingthatJAK2mutationsarenotthedisease-initiatingeventinsomepatients,althoughthefrequencyofthisscenarioremainsunclear.ProgressiontoAcuteMyeloidLeukemiaProgressiontoacutemyeloidleukemia(AML)occursinasmallminorityofETpatientsandinvolvestheaccrualoffurthergeneticevents.

8、DiagnosisandManagementDiagnosticCriteriaMutationsinJAK2exon12arenotthoughttooccurinpatien

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