摘要
本研究探讨急性髓系白血病(AML)患者NPM1基因第12外显子突变的临床特点及其与FLT3-ITD和IDH1突变的相互关系。收集AML患者骨髓标本,收集患者的临床资料,按WHO标准诊断分型。抽提基因组DNA,采用PCR后测序方法检测NPM1突变。结果表明,对389例AML的标本检测发现,NPM1突变的发生率为14.1%(55/389);FLT3-ITD突变的发生率为14.7%(57/389),IDH1突变的发生率为6.4%(25/389)。在AML1-ETO、PML-RARA和CBF-MYH11融合基因的AML中没有发现NPM1突变,NPM1突变组FLT3-ITD和IDH1突变的发生率分别为29.1%和12.7%,显著高于NPM1未突变组的12.3%和5.4%。NPM突变易于发生在正常核型AML中,发生率为26.5%(35/132)。NPM1突变的AML具有发病年龄偏大、血小板数高、易于发生在AML-M5、CD34阳性比例低、易于与FLT3-ITD和IDH1突变伴发等临床特点。NPM1突变阴性组的1个疗程CR率为69.8%,NPM1突变阳性组的1个疗程CR率为72.2%,两组之间无统计学差异(P=0.07)。结论:NPM1突变的AML具有独特的临床特点,易于与FLT3-ITD和IDH1突变共存,而不会与AML1-ETO、PML-RARA和CBF-MYH11融合基因共存。
The puropose of this study was to investigate the clinical characteristics of newly diagnosed acute myeloid leukemia （AML） patients with NPM1 mutation in exon 12 and to explore the relationship between NPM1 mutation and FLT3-ITD,IDH1 mutation.The AML clinical data and bone marrow samples of patients were collected.The diagnosis and classification were based on WHO criteria.The genomic DNA was extracted and NPM1 mutation was detected by sequencing after PCR.The specimens of 389 AML patients were tested.The results showed that the NPM1 mutation was found in 14.1％ samples （55/389）.The incidence of FLT3-ITD mutation was 14.7％ （57/389）.The incidence of IDH1 mutation was 6.4％ （25/389）.NPM1 mutation was not detected in AML with AML1-ETO,PML-RARA or CBFMYH11 fusion genes.The incidences of FLT3-ITD and IDH1 mutation were 29.1％ and 12.7％ respectively in AML with NPM1 mutation.The incidences of FLT3-1TD and IDH1 mutation were 12.3％ and 5.4％ respectively in AML without NPM1 mutation.The incidences of FLT3-ITD and IDH1 mutation were significantly higher in AML with NPM1 mutation than that in AML without NPM1 mutation.The incidence of NPM1 mutation in normal karyotype AML was 26.5％ （35/132） which significantly higher than that in other AML.The AML with NPM1 mutation characterized by older age,high platelet number,higher incidence in AML-M5,lower CD34 positive cells,more possible co-existence with FLT3-ITD and IDH1 mutation and other clinical features.The complete remission rate after one cycle of induction chemotherapy was 69.8 ％ in AML without NPM1 mutation.The complete remission rate after one cycle of induction chemotherapy was 72.2％ in AML with NPM1 mutation,there was no significant difference between them （P =0.07）.It is concluded that AML with NPM1 mutation has distinct clinical features.NPM1 mutation can co-exists with FLT3-ITD and IDH1 mutation,but not with AML1-ETO,PML-RARA or CBF-MYH11 fusion genes.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2014年第1期11-15,共5页
Journal of Experimental Hematology
基金
国家科技重大专项(2011ZX09302-007-04)
卫生公益性行业科研专项(20120217)
国家自然基金(81070427)
