肿瘤学细胞分化课件.ppt

CellDifferentiationCancer肿瘤学细胞分化

细胞分化（differentiation）是指同源细胞逐渐发育成具备稳定形态结构、生理功能和生化特征的另一类型细胞的过程。细胞分化过程是由一系列基因产物（regulatoryproteins）调控的。i.e.,每个基因的表达都必须：在正确的细胞中；在正确的时间；对正确的信号产生正确的反应；产生正确的表达水平。肿瘤学细胞分化

例子：眼形成的关键调控蛋白Ey（果蝇）ey基因早期细胞（发育成腿）腿中眼细胞分化眼形成肿瘤学细胞分化

InductionofPluripotentStemCellsfromAdultHumanFibroblastsbyDefinedFactorsCell2007,131,861-872（Oct3/4,Sox2,Klf4,c-Myc）肿瘤学细胞分化

肿瘤学细胞分化

LeukemiaAcuteChronicLymphoidMyeloidLymphoidMyeloid(CLL)(CML)(ALL)AMLM0M1M2M3M4M5M6M7FAB:肿瘤学细胞分化

M2t(8;21)AML1-ETOM1t(9;22)M5t(9;11)M3t(15;17)PML-RARαacutepromyelocyticleukemia“Acutemyelogenousleukemias(AMLs)aregeneticallyheterogeneousandcharacterizedbychromosomalrearrangementsthatproducefusionproteinswithaberranttranscriptionalregulatoryactivities.”MyriamAlcalayet.al.,2003FAB,TranslocationandFusionProteins肿瘤学细胞分化

M3t(15;17)PML-RARαacutepromyelocyticleukemia“Acutepromyelocyticleukemia(AMLM3)isnowthemostfrequentlycurableacuteleukaemiainadultsifpromptlydiagnosedandadequatelytreated.”ParmarS,TallmanMS.,2003肿瘤学细胞分化

DifferentiationTherapyDifferentiationtherapiesarebroadlydefinedasthosethatinducemalignantreversion(i.e.themalignantphenotypebecomesbenign).Clinically,thesetherapieshavebeenmostsuccessfulforacutepromyelocyticleukemia(APL),withtheuseofall-transretinoicacid(ATRA).Thistreatmenthaschangedacancerwithapreviouslydismaloutcomeintooneofthemosttreatableformsofleukemia.Theexactmechanismsofdifferentiationareunknown—itisunclearifitoccursbyinducingterminaldifferentiation(G0arrest),byinducingdifferentiation‘backwards’tothenon-malignantformofthecell,orbytriggeringapoptosis.ItislikelythatitinvolvesallofthesepathwaysAlexanderISpiraet.Al.,Differentiationtherapy,CurrentOpinioninPharmacology2003肿瘤学细胞分化

1949:describedinF