急性單核細(xì)胞白血病M5a和M5b細(xì)胞遺傳學(xué)與臨床表現(xiàn)的比較

1、急性單核細(xì)胞白血病M5a和M5b細(xì)胞遺傳學(xué)與臨床表現(xiàn)的比擬【摘要】為了比擬急性單核細(xì)胞白血病5a和5b細(xì)胞遺傳學(xué)差異，并研究其與臨床行為之間的互相關(guān)系，采用骨髓直接法和24小時(shí)短期培養(yǎng)法制備染色體標(biāo)本，用G顯帶技術(shù)對58例成人初發(fā)急性單核白血病細(xì)胞進(jìn)展核型分析，同時(shí)對其臨床資料進(jìn)展回憶性研究。結(jié)果說明：58例患者中正常核型28例，異常核型30例，其中正常核型在5b中出現(xiàn)率高于5aP0.0001，異常核型中11q23異常和8染色體在5a中均較5b常見P0.01；臨床上異常核型的5患者常有高白細(xì)胞B計(jì)數(shù)，中樞神經(jīng)系統(tǒng)浸潤，完全緩解(R)率低及存活期明顯縮短的特征。結(jié)論：急性單核細(xì)胞白血病在遺傳和臨

2、床上是一組異質(zhì)性疾病，但5a和5b似乎具有各自獨(dú)特的遺傳學(xué)背景和臨床表現(xiàn)?！娟P(guān)鍵詞】急性單核細(xì)胞白血病；AL-5a；AL-5b；細(xì)胞遺傳學(xué)parisnfytgenetisandlinialanifestatinsbeteen5aand5bfAutenytiLeukeiaAbstratTparetheytgenetidifferenebeteen5aand5bfautenytileukeiaandtstudytherrelatinbeteenkarytypesandlinialanifestatins，attalf58asesfdenvadultAL5havebeeninvestigated.h

3、rseetaphasesfbnearrellserepreparedbyusingdiretethdand24hursshrt-terulture.ThekarytypesereanalyzedbyG-banding.eanhile，linialinfratinftheseaseserestudiedretrspetively.Theresultsshedthatthereere28ithnralkarytypeand30ithaberrantkarytypein58ases.Thefrequenyfnralkarytypeinpatientsith5bassignifiantlyhigher

4、thanthatinpatientsith5a(P=0.0001).The11q23aberratinsandtrisy8erereninpatientsith5ainparisnithpatientsith5b(P0.01).ThepatientsithAL5ithaberrantkarytypehadahigherinidenefhyperleuytsis，extraedullaryentralnervesysteinfiltratin，lerpletereissin(R)rateandshrterverallsurvival.Itisnludedthatautenytileukeiais

5、aseriesfhetergeneusdiseases，adistintiveytgenetifeaturesanbebservedbeteenpatientsithAL5aand5b，theseresultsillprvideinsightsintthelassifiatinandpathgenesisehanisfAL5atleularlevel.Keyrdsautenytileukeia;AL-5a;AL-5b;ytgenetisAuteyelidleukeia(AL)anbelassifiedbyFABsysteintdifferentgrupsbasednellularrphlgya

6、ndytheistrystainingfbnearrells.Ardingtthedifferentiatinstagefnytiells，autenytileukeia(AL-5)nsistsftgrups:5a，theperentagefnblastsis80%;5b，theajrityfnytiellsareprnytesblasts80%1.Inadditin，heatlgialalignaniesanbelassifiedaslyphyti，yelid，histytiandastytiseriesbasedntheriginfalignantellsbytheH.Eahgrupisd

7、eterinedbyrphlgy，ytgenetisandlinialharateristis.Hever，thesetlassifiatinsystesanntbeusedtdifferentiatetheytgenetiharateristisandlinialanifestatinsbeteenpatientsith5aand5b.Inthepresentstudy，einvestigated58nelydiagnsedAL5patientsinrdertbetterharaterizetheytgenetihangesandlinialanifestatinsfthesepatient

8、sfrreauratelassifiatinandunderstandingfthepathgene-sisfthedisease，hihuldleadtthedevelpentfanveltherapeutistrategy.aterialsandethdsPatientsDuringtheperidfrJanuary2000tJune2022，58patientserenelydiagnsedithAL5inthedepartentfHeatlgyfUninHspitalaffiliatedtTngjiedialllege，HuazhngUniversityfSieneandTehnlgy

9、(uhan).Thelinialrerdsandlabratrytestreprtsftheseasesererevieed.Thelinialdiagnsisasadebasednthelinialsypts，peripheralbldunts，bnearrexainatin.26utfthe58patientserelassifiedas5aand32as5b.Thereere12alesand14fealesfAL5apatients，agedfr18t59ithaedianagef39.5，hile20alesand12fealesfAL5bpatientsagedbeteen28t6

10、6ithaedianagef48.ytgenetianalysis2-3lsfheparinizedbnearrfrpatientsereulturedinRPI1640suppleentedith20%fetalalfseruand20U/lheparin.Theelldensityasadjustedt1106/l.Thesaplesereinubatedat37fr24hurs，thentreatedbylhiinesiththefinalnentratinf0.05g/lfranther42inutes.Standardytgenetipreparatinasade;adifiedhr

11、sebandingtehnique(G-banding)asused.Frhrseanalysisatleast30-50etaphasehrsesshuldbeuntedineahsaple，and10etaphasehrsesereanalyzedbyirspyrirphtgraphy.KarytypesereanalyzedardingttheInternatinalSystefrytgenetiNenlature(ISN.1995).PrtlsAllpatientseretreatedithregiensasflls:(1)DA(daunrubiin45g/2perdaybyintra

12、venusinfusin(iv)，day1t3，plusytarabine100-200g/2perdaybyintrausularinjetin(i)day1t7);(2)HA(hharringtnine2-3g/2byivperday，day1t3，plusytarabine100-200g/2perdaybyi，day1t7);(3)IA(idarubiin10g/2perdaybyiv，day1t3，plusytarabine100-200g/2perdaybyiday1t7);(4)EA(itxantrne8-12g/2perday，day1t3，plusetpside100g/2p

13、erdaybyivdrip，day4t5，plusytarabine100-200g/2perdaybyi，day1t5).Subsequently，sepatientsreEivedstrengtheninghetherapyithytarabine1.5g/2tieadayfr6days，hilepatientslderthan70yearsreeivedthesaetherapyfrnly3days.utfthe58patients，tunderenthuanleukyteantigen-athedallgeneibnearrtransplantatinandneunderentperi

14、pheralbldsteelltransplantatinafterthediseasesentintpletereissin.Definitinfrespnsepletereissinasdefinedineahprtlasabsenefleukeiainthebnearrindiatedbylessthan5%blasts，reveryfnralperipheralbldelluntsasindiatedbyabsluteneutrphilunt1.5109/L，andplateletunt100109/L，andabsenefextraedullaryleukeia.Statistial

15、analysislinialandytgenetiharateristisfAL5apatientsereparediththatfAL5bpatientsusing2test.Resultsytgenetianalysislinialharateristisutfallthepatients，abnrallyhighhitebldellunts(50109/L)eredetetedin27patients(5avs5b14vs13);hepatsplenegalyasbservedin22patients(5avs5b11vs11);extraedullarydiseaseintheskin

16、asfundin16patients(5avs5b9vs7)，enlargeentflyphndesin20patients.15patientshadentralnervussysteleukeia(5avs5b9vs6);14patientshadthedisseinatedintravasularagulatin(5avs5b8vs6).Thepletereissinrateas42.3%(n=11)frpatientsith5a，56.3%(n=18)frpatientsith5b，and50%(n=29)frallAL5patients.Theperentagefthene-year

17、disease-freesurvivalDFSinpatientsithAL5aas26.9%(n=7)，hileitas34.4%(n=11)inpatientsithAL5b.Thelinialharateristisbeteenthetsubtypeserentsignifiantlydifferent(P0.05).TheseresultsarelistedinTable2.Table1.ytgenetidatafrpatientsithAL5subtypes略Table2.linialharateristisfAL5patientsithvariuskarytypes略Disussi

18、nSpeifinn-randhrsalabnralitiesareftenbservedinertainsubtypesfheatlgialignany.reaberrantytgenetishasbeendisveredinpatientsithAL5afterinitiallyfindingft(9；11)(p21；q23)in5apatientbyBerger2in1980.Haferlahetal3nsideredthat11q23aberratinandtrisy8eresignifiantlyassiatedithAL-5.Tkahuketal4fundthat11q23abnra

19、litiesareinvlvedintheLLgene(rnaed“ALL1r“HRX)，spanning90kbfDNAandendinga3968-ainaidprtEinithleularassabut430kD.Theild-typeLLprteinhasthreeAT-hkDNAbindingdainsandultiplezinfingerdains.LLgene-endedprdutasatransriptinfatrthenaybindiththegenesregulatingbdydevelpentandelldifferentiatin5.Thegenerearrangeen

20、tsfLLsuhas11q23translatinalteritsstrutureandfuntinandayleadtleukegenesis.eanhile，thetrisy8isahrseabnrality.Althughtheinduingehanisandthebilgirlefthetrisy8areunknn，therelatinshipbeteenthetrisy8andnytialignanyhasbeensuggested6.Theurreneftrisy8ayenhanetheexpressinfgenes，leadingtthedevelpentfleukeias.In

21、thisstudy，theinidenef“nralkarytypesashigherinpatientsith5bthanthatinpatientsith5a(P0.001);theinvlveentf11q23aberrantinsandtrisy8eredetetedrefrequentlyinpatientsith5athanthatith5b(P0.01)inardaneithprirstudies3，6.Theseresultsindiatethatthegeniinstabilityisrenandplexin5apatientleukeiellsthanthatin5bell

22、s.ThelinialharateristisfpatientsithAL5inludedextraedullaryinfiltratinithhighBunts，lpletereissinrateandshrtdisease-freesurvival(DFS).Inurstudy，nsignifiantdiffereneasfundregardingthseharateristisbeteenthetsubtypes，inagreeentiththeresultsfrthestudyftheEasternperativenlgyGrup(EG)n81patientsithAL51.eanti

23、e，Shhetal7analyzed1897ALasesith11q23abnralities，andfundthatthepatientsith11q23deletin/translatin/inversinereftenslightlyyungerandhadhighBunts，hepatsplenegaly，entralnervussysteinvlveent，lpletereissinandshrtDFS.ThelinialdatafrtheSuthestnlgyGrup8denstratedthatthepatientsiththetrisy8ereslightlylder，andi

24、thlerBunts，lerperentagesfperipheralblasts，lerpletereissinandshrterDFSthanthsefpatientsithutthetrisy8.Beauseftheliitedasenubers，theparisnflinialdataangpatientsithvariusaberrantkarytypesasntperfredinthisstudy，butlerpletereissinandshrterDFSerestillevident.Innlusin，theAL5patientsexainedinthisstudyshedas

25、ignifianthetergeneityinytgenetisandlinialanifestatins.The11q23aberrantinsandtrisy8ererefrequentlydetetedinpatientsithAL5a，paredithpatientsith5b.stfthepatientsithAL5bhadanralkarytype.ThepatientsithaberrantkarytypeshadalerpletereissinrateandshrterDFS.Theseresultsprvidefurtherinsightsintthepathgenesisf

26、AL5andightleadtabetterlassifiatinfthedisease.AknledgeentsTheauthrsuldliketthankPrfessrDahngZhuinedialUniversityfSutharlina，USA，frhelpfulEnglishplishingntheanusript.【參考文獻(xiàn)】1TallanS，KiHT，PaiettaE，etal.Autenytileukeia(Frenh-Aerian-Britishlassifiatin5)desnthavearseprgnsisthanthersubtypesfauteyelidleukeia:areprtfrtheEasternperativenlgyGrup.Jlinnl，2022；22:1276-12862BergerR，BernheiA，ehHJ，etal.ytgenetisstudiesnautenytileukeia.LeukRes，1980；4