Profiling B cell chronic lymphocytic leukemia by reverse phase protein array: Focus on apoptotic proteins

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: signal transduction;    lymphocyte;    HSP70;    Smac/DIABLO;   

DOI  :  10.1189/jlb.2AB0715-301R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Bcellchroniclymphocyticleukemia(CLL)ischaracterizedbytheaccumulationofBlymphocytesfromproliferativeactivityandapoptosisresistance.TheincreasedawarenessoftheimportanceofBcellreceptorsignalinginCLLhasraisednewopportunitiesfortargetedintervention.Herein,wedescribeastudyperformedwiththehigh‐throughputRPPA(reversephaseproteinarray)technique,whichallowedustosimultaneouslystudydifferentmoleculesinalargeseriesofpatients.WeanalyzedBlymphocytesfrom57patientswithCLLand11healthysubjects.Differentpathwayswereassessedforactivation/expressionofkeysignalingproteins.DataobtainedwerevalidatedbyWesternblottingandconfocalmicroscopy.TheRPPAinvestigationanditsvalidation,identified3seriesofproteins:1)moleculeswhoseexpressionlevelsreachedstatisticallysignificantdifferencesinCLLvs.healthycontrols(HSP70,Smac/DIABLO,cleavedPARP,andcleavedcaspase‐6);2)proteinswithapositivetrendofdifferenceinCLLvs.healthycontrols(HS1,γ‐tubulin,PKCα/β‐IIThr‐638/641,p38MAPKThr‐180/Tyr‐182,NF‐κBSer‐536,Bcl2Ser‐70andSrcTyr‐527);and3)moleculesdifferentiallyexpressedinpatientswithIGHVmutationsvs.thosewithoutmutations(ZAP70,PKC‐ζλ,Thr‐410/403,andCD45).Thisstudyidentifiedsomemolecules,particularlythoseinvolvedinapoptosiscontrol,whichcouldbeconsideredforfurtherstudiestodesignnewtherapeuticstrategiesinCLL...

【 授权许可】

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