OBJECTIVE SNPs in lnc RNAs may alter the expression or secondary structure of lnc RNAs and then impact their functions.Whether lnc RNA SNPs affect the prognosis of acute myeloid leukemia(AML)remains unknown.To search ...OBJECTIVE SNPs in lnc RNAs may alter the expression or secondary structure of lnc RNAs and then impact their functions.Whether lnc RNA SNPs affect the prognosis of acute myeloid leukemia(AML)remains unknown.To search the association between lnc RNA SNPs and AML outcomes,thirty tag SNPs in GAS5,H19,MALAT1,WT1-as and SRA were genotyped in313 AML patients.METHODS Survival analysis was performed in both AML patients recruited presently and GEO samples.The expression of GAS5 and TP63 was analyzed by real-time quantitative PCR.Dual-luciferase reporter gene assay was used to confirm the interactions between GAS5 rs55829688 and TP63.RESULTS Survival analysis indicated that rs55829688(T>C),located in GAS5 promoter,was significantly associated with the prognosis of AML.The average overall survival(OS)for patients with the rs55829688 CC genotype was significantly shorter than those carrying the rs55829688 T allele(P=0.018).Patients with rs55829688 CC genotype showed higher GAS5 expression in PBMCs than carriers of rs55829688T allele(P=0.025).Rs55829688 CC homozygotes also harbored a longer platelets recovery than those with rs55829688 T allele(P=0.040).In vitro study showed that GAS5 promoter harboring the rs55829688 C al ele showed marginal y increased reporter gene activity(P=0.054),and the promoter activity was increased by TP63 in a dose-dependent manner(P=0.001).Moreover,GAS5 expression was associated with AML OS in the GEO GSE12417 dataset,and GAS5 higher expression predict shorter OS(P=0.011).CONCLUSION Rs55829688 polymorphism could increase GAS5 expression by interacting with TP63 and was associated with worse OS in Chinese AML patients.展开更多
OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT...OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.展开更多
基金The project supported by National Natural Science Foundation of China(81422052,81403017)Special Topic of the Major Subject of National Science and Technology(2012ZX09509-339107)+1 种基金Hunan Provincial Natural Science Foundation of China(13JJ1010)by Funds for Hunan Education Department Program(12K006)
文摘OBJECTIVE SNPs in lnc RNAs may alter the expression or secondary structure of lnc RNAs and then impact their functions.Whether lnc RNA SNPs affect the prognosis of acute myeloid leukemia(AML)remains unknown.To search the association between lnc RNA SNPs and AML outcomes,thirty tag SNPs in GAS5,H19,MALAT1,WT1-as and SRA were genotyped in313 AML patients.METHODS Survival analysis was performed in both AML patients recruited presently and GEO samples.The expression of GAS5 and TP63 was analyzed by real-time quantitative PCR.Dual-luciferase reporter gene assay was used to confirm the interactions between GAS5 rs55829688 and TP63.RESULTS Survival analysis indicated that rs55829688(T>C),located in GAS5 promoter,was significantly associated with the prognosis of AML.The average overall survival(OS)for patients with the rs55829688 CC genotype was significantly shorter than those carrying the rs55829688 T allele(P=0.018).Patients with rs55829688 CC genotype showed higher GAS5 expression in PBMCs than carriers of rs55829688T allele(P=0.025).Rs55829688 CC homozygotes also harbored a longer platelets recovery than those with rs55829688 T allele(P=0.040).In vitro study showed that GAS5 promoter harboring the rs55829688 C al ele showed marginal y increased reporter gene activity(P=0.054),and the promoter activity was increased by TP63 in a dose-dependent manner(P=0.001).Moreover,GAS5 expression was associated with AML OS in the GEO GSE12417 dataset,and GAS5 higher expression predict shorter OS(P=0.011).CONCLUSION Rs55829688 polymorphism could increase GAS5 expression by interacting with TP63 and was associated with worse OS in Chinese AML patients.
基金The project supported by National Naural Science Foundation of China(81422052)Special Topic of the Major Subject of National Science and Technology(2012ZX09509-107)Hunan Provincial Natural Science Foundation of China(13JJ1010)
文摘OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)patients.METHODS DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern China.AML patients underwent combined chemotherapy with cytarabine and anthracyclines.Overall survival(OS)and Disease-free survival(DFS)as major end points were defined.The prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard model.RESULTS We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were observed.CONCLUSION DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.
