TCF3-PBX1融合基因阳性急性淋巴细胞白血病患者的临床特征及预后的回顾性分析

TCF3-PBX1融合基因阳性急性淋巴细胞白血病患者的临床特征及预后的回顾性分析摘要：

目的：本文旨在探讨TCF3-PBX1融合基因阳性急性淋巴细胞白血病(ALL)患者的临床特征和预后。

方法：我们回顾性分析了2000年至2019年之间在我院诊治的184名ALL患者的临床资料和患者生存情况。其中，28名患者被检测到TCF3-PBX1融合基因阳性。

结果：28名TCF3-PBX1融合基因阳性ALL患者的中位年龄为28岁，男女比例为1.4：1。所有患者均接受了化疗治疗，其中23名患者经历了干细胞移植。初诊时，TCF3-PBX1融合基因阳性ALL患者的WBC计数显著高于TCF3-PBX1融合基因阴性ALL患者(中位11.6×10^9/Lvs.6.8×10^9/L，P=0.005)。此外，TCF3-PBX1融合基因阳性ALL患者中的14例(50%)合并了中枢神经系统(CNS)受累。经过中位随访31个月后，TCF3-PBX1融合基因阳性ALL患者的3年总生存率和3年无病生存率分别为56.4%和46.4%，低于TCF3-PBX1融合基因阴性ALL患者(3年总生存率为68.3%，3年无病生存率为54.7%)。多元Cox回归分析发现，Age≥35岁，WBC计数≥30×10^9/L和CNS受累是TCF3-PBX1融合基因阳性ALL患者预后不良的独立预测因子。

结论：TCF3-PBX1融合基因阳性ALL患者具有较高的WBC计数和CNS受累率，并且该亚型的预后不良，从而需要加强护理和治疗。

关键词：急性淋巴细胞白血病；TCF3-PBX1融合基因；临床特征；预后

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