白血病相关shp-2激活突变可能促进白细胞浸润及多器官损伤-leukemia - related shp - 2 activation mutation may promote leukocyte infiltration and multiple organ damage.docxVIP

leukemia.Afterourresearchgroupreceivedthemodelmice,wemainlyworkforthefollowingtasks:1.Iftherearemicewithmyeloidproliferativedisease,willtheleukocytshighproliferativeresponsivetotheexistenceofIL3?2.Istheleukocyteadhesionandmigrationcapacityofmiceincreasing?Arethesecretionofinflammatorycytokinesontherise?Namely,whetherthereisleukocyteinfiltrationwhichledtomultipleorganinjury;3.Canithappentoleukemia?Whatistherelationbetweenthebiologicalbehaviorofmalignantandleukemia?Therefore,thisstudyisusingofmodelmicewhichhaveSHP-2D61Ggain-of-functionmutationtoobservethelekucytswhichexpressSHP-2inphysiologicallevelbuthavegain-of-functionmutation.Weinvestigatethecells’changeofabilityinadhesion,invasionanditseffecttoorgandamage,andthepossiblepreliminarystudyofmolecularmechanisms.Theresultsshowedthat,SHP-2D61G/+mutantmiceactivatedleukocyteadhesion,migrationcomparedwiththecontrolwild-typemice(WT)significantlyincreased;inmutantmice,theexpressionofIL-2andTNF-αmRNAfromleukocytewassignificantlyhigherabundance,IL-2,TNF-αconcentrationsincreasedaccordinglyinthesupernatant;furtherly,wefoundthelevelsofaminotransferase(ALT)andcardiactroponinI(CTni)inserumweresignificantlyhigherinmutantmousethanthecontrolmice;leukocyteinfiltrationintheliver,spleenandlungtissueincreased,appearedhistologicalchangesasinflammatoryinjurytype;theresearchformechanisminmutantmicefoundthatthetransferofNF-κBsignificantlyincreasedinleukocyts.TheseresultspromptSHP-2gain-of-functionmutationsmayatleastthroughtheenhancedNF-κBsignalingpathway,thenpromoteleukocyteadhesion,andinvasiontovarioustissuesandorgans,whileenhancetheabilityofsecretinginflammatoryfactors,mediatetosignificanttissuedamage.Theresultsprovidesomecluesforstudytheclinicalleukemiapatientswhyeasilyappearthemechanismofmultipleorganfailure.KeyWords：SHP-2/MODS/leukemia/Gain-of-functionmutation英文缩略表（abbreviations）英文缩写Amp英文全名Ampicillin中文全名氨苄青霉素PMSFphenylmethylsulfonylfluoride苯甲基磺酰氟DTTDithiotheitol二硫苏糖醇Bpbasepair碱基对BSAbovineserumalbumin牛血清白蛋白cDNAcomplementarydeoxyribonuclei