多发性骨髓瘤 英文介绍【18页】.pptx

MultipleMyelomaPlasmacellmalignancyAbout300newcasesinNorwayeachyearIncurableMeansurvivalafterdiagnosis:3-4yearsMalignantplasmacellsfoundinthebonemarrowOsteolyticlesionscommoncomplication

Chromosomal-translocationsassociatedwithhumancancerUncommonincancersderivedfromepithelialtissues(whichcomprises80%ofhumantumores)FoundintumoursderivedfrommesenchymaltissuesOfteninhaematologicalcancersasaby-productofnaturalDNArecombinationthattakeplacetogenerateantigen-receptorsInB-celltumours(ALL,CLL,Lymfoma,MultipleMyeloma)-translocationsinvolvingIgheavychaingenes(14q32)InT-celltumours(ALL,Lymfom)-OftentranslocationsinvolvingtheTCRdeltachain(14q11)

DifferentiationandmaturationintheB-celllineage

BoneMarrowMULTIPLEMYELOMAG,A,EPlasmacellVirginBcellLymphoblastLymphoplasmacytePlasmablastGerminalCenterSOMATICPre-BcellIgMHYPERMUTATIONWALDENSTROM’SCLLBURKITT’SLYMPHOMAFOLLICULARLYMPHOMALymphnodeALLOverviewofcancersderivedfromcellsatvariousstagesinthetheB-celllineage

TranslocationsinvolvingtheIgHlocus(14q23)inmultiplemyeloma:Multiplemyelomaiscancerduetotransformationofplasmacells(antibody-producingcells).InabouthalfofthesetumourstranslocationsinvolvingtheIgHlocusasonepartnerisfound.ThesetranslocationsresultsincellulargenesinvolvedgrowthcontrolcomeundercontroloftheIgenhancer,resultinginaberrantexpressionofthesegenes.FromL.Bergsagel2001http://myeloma

ProgressivegeneticeventsalsoinmultiplemyelomaactivatingmutationsN,K-rasFGFR3p53mutationkaryotypicinstabilityMGUSIntra-medullaryMyelomaExtra-medullaryMyelomaNormalPlasmablast13q12-14monosomy/deletionIgHtranslocationc-myctranslocation

Bonemarrowaspirateformamultiplemyelomapatient

TransmembraneShedSyndecan-1Heparansulfateproteoglycan

Seideletal.Blood2000Apr1;95(7):2197sSyndecan-1inseraofpatientswithmultiplemyeloma

Seideletal.Blood.1998Feb