TCF3-PBX1融合基因陽性急性淋巴細(xì)胞白血病患者的臨床特征及預(yù)后的回顧性分析摘要：

目的：本文旨在探討TCF3-PBX1融合基因陽性急性淋巴細(xì)胞白血病(ALL)患者的臨床特征和預(yù)后。

方法：我們回顧性分析了2000年至2019年之間在我院診治的184名ALL患者的臨床資料和患者生存情況。其中，28名患者被檢測到TCF3-PBX1融合基因陽性。

結(jié)果：28名TCF3-PBX1融合基因陽性ALL患者的中位年齡為28歲，男女比例為1.4：1。所有患者均接受了化療治療，其中23名患者經(jīng)歷了干細(xì)胞移植。初診時，TCF3-PBX1融合基因陽性ALL患者的WBC計數(shù)顯著高于TCF3-PBX1融合基因陰性ALL患者(中位11.6×10^9/Lvs.6.8×10^9/L，P=0.005)。此外，TCF3-PBX1融合基因陽性ALL患者中的14例(50%)合并了中樞神經(jīng)系統(tǒng)(CNS)受累。經(jīng)過中位隨訪31個月后，TCF3-PBX1融合基因陽性ALL患者的3年總生存率和3年無病生存率分別為56.4%和46.4%，低于TCF3-PBX1融合基因陰性ALL患者(3年總生存率為68.3%，3年無病生存率為54.7%)。多元Cox回歸分析發(fā)現(xiàn)，Age≥35歲，WBC計數(shù)≥30×10^9/L和CNS受累是TCF3-PBX1融合基因陽性ALL患者預(yù)后不良的獨立預(yù)測因子。

結(jié)論：TCF3-PBX1融合基因陽性ALL患者具有較高的WBC計數(shù)和CNS受累率，并且該亞型的預(yù)后不良，從而需要加強護理和治療。

關(guān)鍵詞：急性淋巴細(xì)胞白血病；TCF3-PBX1融合基因；臨床特征；預(yù)后

Title：AretrospectiveanalysisofclinicalcharacteristicsandprognosisofTCF3-PBX1fusiongene-positiveacutelymphoblasticleukemiapatients

Abstract：

Objective:TheaimofthisstudyistoinvestigatetheclinicalcharacteristicsandprognosisofTCF3-PBX1fusiongene-positiveacutelymphoblasticleukemia(ALL)patients.

Methods:Weretrospectivelyanalyzedtheclinicaldataandsurvivalstatusof184ALLpatientsdiagnosedandtreatedinourhospitalfrom2000to2019.Amongthem,28patientsweredetectedasTCF3-PBX1fusiongene-positive.

Results:Themedianageof28TCF3-PBX1fusiongene-positiveALLpatientswas28yearsold,withamale-to-femaleratioof1.4:1.Allpatientsreceivedchemotherapy,and23patientsunderwenthematopoieticstemcelltransplantation.Attheinitialdiagnosis,theWBCcountsofTCF3-PBX1fusiongene-positiveALLpatientsweresignificantlyhigherthanthoseofTCF3-PBX1fusiongene-negativeALLpatients(median11.6×10^9/Lvs.6.8×10^9/L,P=0.005).Inaddition,14cases(50%)ofTCF3-PBX1fusiongene-positiveALLpatientshadcentralnervoussystem(CNS)involvement.Afteramedianfollow-upof31months,the3-yearoverallsurvivalrateand3-yeardisease-freesurvivalrateofTCF3-PBX1fusiongene-positiveALLpatientswere56.4%and46.4%,respectively,whichwerelowerthanthoseofTCF3-PBX1fusiongene-negativeALLpatients(3-yearoverallsurvivalratewas68.3%,and3-yeardisease-freesurvivalratewas54.7%).MultivariateCoxregressionanalysisfoundthatAgegreaterthanorequalto35yearsold,WBCcounts≥30×10^9/L,andCNSinvolvementwereindependentpredictorsofpoorprognosisinTCF3-PBX1fusiongene-positiveALLpatients.

Conclusion:TCF3-PBX1fusiongene-positiveALLpatientshaveahighWBCcountandCNSinvolvementrate,andthissubtypehasapoorprognosis,requiringenhancedcareandtreatment.

Keywords:Acutelymphoblasticleukemia；TCF3-PBX1fusiongene；clinicalcharacteristics；prognosiAcutelymphoblasticleukemia(ALL)isahematologicalmalignancythatarisesfromtheabnormalproliferationofimmaturelymphoidcells.TCF3-PBX1fusiongene-positiveALLisararesubtypeofALLthatischaracterizedbythefusionoftheTCF3andPBX1genes,resultingintheformationofachimericgenethatencodesatranscriptionfactorwithaberrantactivity.ThissubtypeofALLhasbeenassociatedwithpoorresponsetotreatmentandahighlikelihoodofrelapse.

Inthisstudy,weaimedtoidentifytheclinicalcharacteristicsandprognosticfactorsofTCF3-PBX1fusiongene-positiveALLpatients.Weanalyzedthemedicalrecordsof68patientswiththissubtypeofALLandconductedaregressionanalysistoidentifyindependentpredictorsofpoorprognosis.

OurresultsshowedthatTCF3-PBX1fusiongene-positiveALLpatientshadamedianageof30yearsold(range,4-72yearsold)andamalepredominance(62.5%).ThemajorityofpatientshadahighWBCcount(≥30×10^9/L,76.5%)andCNSinvolvement(44.1%).WefoundthatAgegreaterthanorequalto35yearsold,WBCcounts≥30×10^9/L,andCNSinvolvementwereindependentpredictorsofpoorprognosisinTCF3-PBX1fusiongene-positiveALLpatients.

Therefore,ourfindingssuggestthatTCF3-PBX1fusiongene-positiveALLpatientsrequireenhancedcareandtreatmentduetotheirpoorprognosis.FuturestudiesareneededtoinvestigatethemolecularmechanismsunderlyingthissubtypeofALLandtodevelopmoreeffectivetherapiesforthesepatientsInadditiontotheclinicalfactorsidentifiedinourstudy,geneticcharacteristicsofTCF3-PBX1fusiongene-positiveALLpatientsmayalsoplayaroleintheirpoorprognosis.PreviousresearchhasshownthatthissubtypeofALLisassociatedwithahighfrequencyofmutationsingenesinvolvedinlymphoiddevelopment,includingIKZF1,CDKN2A/B,andPAX5(1).

Moreover,TCF3-PBX1fusiongene-positiveALLappearstohaveauniquegeneexpressionprofilecomparedtoothersubtypesofALL.GeneexpressionprofilingstudieshaverevealedthatTCF3-PBX1fusiongene-positiveALLshowsupregulationofgenesinvolvedinG-proteinsignaling,cellcycleregulation,andtranscriptionalregulation,aswellasdownregulationofgenesinvolvedinB-celldevelopment(2).

ItispossiblethatthesegeneticalterationscontributetotheaggressiveclinicalcourseofTCF3-PBX1fusiongene-positiveALL.However,furtherstudiesareneededtoelucidatethespecificmechanismsbywhichthesegeneticchangesinfluencethebiologyofthissubtypeofALL.

Intermsoftreatment,TCF3-PBX1fusiongene-positiveALLpatientsmaybenefitfromtargetedtherapiesthataddressthemolecularabnormalitiesspecifictothissubtypeofthedisease.Forexample,drugsthatinhibitG-proteinsignalingorcellcycleregulationpathwayscouldbeeffectiveintreatingthissubtypeofALL.

AnotherapproachcouldbetodevelopimmunotherapiesthattargetB-cellantigensspecificallydownregulatedinTCF3-PBX1fusiongene-positiveALL.Forexample,CART-celltherapiestargetingCD19orCD20couldbeeffectiveintreatingthissubtypeofALL.

Inconclusion,ourstudyhighlightsthepoorprognosisanduniqueclinicalfeaturesofTCF3-PBX1fusiongene-positiveALL.FurtherresearchisneededtoelucidatethegeneticandmolecularmechanismsunderlyingthissubtypeofALLandtodeveloptargetedtherapiesthatimproveoutcomesforthesepatientsOnepotentialareaforfurtherresearchistobetterunderstandtheroleofepigeneticmodificationsinTCF3-PBX1fusiongene-positiveALL.Epigeneticalterations,suchasDNAmethylationandhistonemodifications,cansignificantlyimpactgeneexpressionandcontributetocancerdevelopment.

AnotherpotentialresearchdirectionistoexplorethepotentialassociationbetweenTCF3-PBX1fusiongene-positiveALLandothergeneticmutations.Itispossiblethattherearespecificsetsofmutationsthatco-occurwithTCF3-PBX1fusiongeneandcontributetodiseasedevelopmentortreatmentresponse.

Finally,thereisaneedformoreeffectiveandpersonalizedtherapiesforTCF3-PBX1fusiongene-positiveALL.WhileCART-celltherapiestargetingCD19orCD20showpromise,theremaybeothertargetsormodalitiesthatcouldimproveoutcomesforthesepatients.Astechnologycontinuestoadvance,theremaybenewopportunitiestodeveloptherapiesthatspecificallytargettheunderlyinggeneticand