慢性粒细胞白血病ChronicMyeloidLeukemiaThe2ndHospitalofShanxiMedicalUniversityHematologyDepartmentIsleukemiafarfromourlife?Isleukemiareallyterrible?Canleukemiabecured?Dotheyneedtoacceptthebonemarrowtransplantation?Isitusefultodiagnoseitearlier?2AtypicalcasereportPatient,Ma**,male,54yearsold,maincomplain“physicalexaminationfoundleucocytosis,splenomegalyfor1week”.Physicalexamination:nojaundice,noenlargedlymphnodes,nobleeding,sternalpalpation+,mediumsplenomegaly.3Atypicalcasereport血常规白细胞350×109/L，血红蛋白98g/L，血小板960×109/L，中性粒细胞95%。正常外周血涂片100×患者外周血涂片100×What’swrongwithhimMainmanifestations:高白细胞，高血小板，轻度贫血脾脏肿大轻微乏力、没有发热、骨痛脾大splenomegaly白细胞高leucocytosis白血病？leukemia5骨髓象：原始细胞＜5%（100×）6骨髓穿刺Whatcanwedonextstep?7DiagnosisCML！Isitreallyterrible?Doesitmeandeath?慢性粒细胞白血病(CML)Professionalwords慢性期CML-CP（ChronicPhase）加速期CML-AP（AcceleratedPhase)急变期CML-BP（BlastPhase）白血病增多(Leucocytosis)脾脏肿大(Splenomegaly)费城染色体(PhiladelphiaChromosome)融合基因(FusionGene)8(一)定义(Definition)CMLisakindofmalignant(恶性)myeloproliferative（骨髓增殖）diseasehappenedintheearlypluripotenthematopoieticstemcellsphase（多能造血干细胞）andismainlyconcernedwithmyeloiddevelopment,developsrelativelyslow.9（二）概况（Introduction）10Itoccursatallages(incidenceof0.036-0.099case/millionpopulation,medianage50-60years,male/femaleratioequal).TheimportantlandmarksofCMLwerethediscoveryofthePhiladelphia(Ph)chromosomeandthecharacterizationoftheBCR/ABLfusiongene.ThreephasesChronicPhaseAcceleratedPhaseAcutePhase自然病程（Naturalhistory）1-4yearsSeveralmonths11“Thefindingssuggestacausalrelationshipbetweenthechromosomeabnormalityobservedandchronicgranulocyticleukemia.”-----PeterNowellfromUniversityofPennsylvaniainPhiladelphia,1960(三)病理生理学Pathophysiology12费城染色体模式图Fig1.FormationofthePhiladelphiachromosomeresultinginaBCR/ABLfusiongenethatgeneratesafusionprotein(P210)responsibleforthechronicMyeloidleukemiaphenotype13Fig2.ThePhiladelphiaChromosome14Fig3.InterphasefluorescenceinSituHybridisationusingprobesforBCRgeneandABLgenes.15Fig4.APCRamplificationdetectingthejunctionofthefusiongeneBCR/ABLinacaseofCMLsuppressapoptosisandpromoteexcesscellproduction(increasedtyrosinekinaseactivity)Figure5.FormationofthePhiladelphiachromosomeresultinginaBCR/ABLfusiongenethatgeneratesafusionprotein(p210)responsibleforthechronicmyeloidleukemiaphenotype.1617（四）临床表现（ClinicalManifestations）1慢性期CML-CP（ChronicPhase）2加速期CML-AP（AcceleratedPhase）3急变期CML-BP（BlastPhase）（四）临床表现（ClinicalManifestations）1慢性期CML-CP（ChronicPhase）（1）Hypermetabolism（高代谢）,weak,fever;（2）Splenomegaly,1/2patientswillbehepatomegaly;（3）Sternalpalpation+,（4）leucocytosis,leukocytestasis181慢性期CML-CP（ChronicPhase）19(5)Blastcells＜10%,eosinophilosis（嗜酸细胞增多）,basocytosis（嗜碱细胞增多）;(6)95%patientshavePhchromosome，fusiongeneBCR/ABL（+）正常骨髓10×CML10×CML100×Fig6.massivespleeninCML20Fig7.Autopsyshowingmassivehepatosplenomegaly（四）临床表现(ClinicalManifestations)2加速期CML-AP（AcceleratedPhase）(1)Feverbutnoreason,anemia,aggravatedbleedingorpain;(2)Progressiveenlargementofthespleen;>20%basophilinperipheralblood;(3)Thrombocytopeniaorreducedbutnoreason;(4)Drugresistance;(5)Theemergenceofnewchromosomeabnormalities:+8,doublePh1chromosome,i17q21(四)临床表现(ClinicalManifestations)3急变期CML-BP（BlastPhase）22•为终末期，表现类似急性白血病；•预后极差，数月内死亡；CML10×CML100×2324
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