共查询到20条相似文献,搜索用时 750 毫秒
1.
Jiang Lin Qin Chen Jing Yang Jun Qian Zhao-qun Deng Wei Qian Xing-xing Chen Ji-chun Ma Dong-sheng Xiong Yu-juan Ma Cui An Chun-yan Tang 《Leukemia research》2014
DEAD box polypeptide 43 (DDX43), a cancer/testis antigen (CTA), has been found to be overexpressed in various solid tumors and some hematologic malignancies. In the present work hypomethylation of the DDX43 gene was detected in 15% (32/214) of primary acute myeloid leukemia (AML) using real-time quantitative methylation-specific PCR (RQ-MSP). The level of DDX43 expression was correlated with DDX43 hypomethylation (R = 0.277, P = 0.014). Moreover, bisulfite sequencing confirmed the significant correlation between the methylation density and the level of DDX43 hypomethylation. Additionally, restoration of DDX43 expression in the K562 cell line by 5-aza-2′-deoxycytidine treatment confirmed a direct contribution of methylation in regulating the DDX43 gene. DDX43 hypomethylation was observed more frequently in favorable group (21.4%) and intermediate group (15.8%) than in poor group (0%) (P = 0.009). AML patients with DDX43 hypomethylation had a better overall survival (median not obtained) than those with DDX43 methylation (median 8 months, 95% confidence interval 5.6–10.4 months) (P = 0.014). In summary, the DDX43 gene is activated by promoter hypomethylation and DDX43 hypomethylation may be a favorable prognostic factor in AML. 相似文献
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Naoki Mori Kentaro YoshinagaKaori Tomita Mari OhwashiToshiaki Kondoh Hanae ShimuraYan-Hua Wang Masayuki ShisekiMichiko Okada Toshiko Motoji 《Leukemia research》2011,35(4):516-521
We performed methylation specific PCR analysis on the RIZ1 promoter in MDS and AML. Methylation was detected in 17 of 34 MDS (50%) and 22 of 72 AML (31%) (p = 0.053). Methylation was detected in eleven of 17 secondary AML from MDS (65%), and eleven of 55 de novo AML (20%) (p = 0.0005). Bisulfite sequence revealed methylation at many CpG sites in the promoter. Decreased RIZ1 expression was accompanied by methylation in six of nine samples examined, while it was also observed in seven of 13 without methylation. Treatment of AML cells, that have RIZ1 methylation, with 5-Aza-dC, induced growth suppression with RIZ1 restoration. Our results suggest that the RIZ1 gene is inactivated in MDS and AML in part by methylation, whereas another mechanism should be involved in others. 相似文献
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GPX3 hypermethylation serves as an independent prognostic biomarker in non-M3 acute myeloid leukemia
Jing-Dong Zhou Dong-Ming Yao Ying-Ying Zhang Ji-Chun Ma Xiang-Mei Wen Jing Yang Hong Guo Qin Chen Jiang Lin Jun Qian 《American journal of cancer research》2015,5(6):2047-2055
Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various solid tumors. However, the pattern of GPX3 promoter methylation in acute myeloid leukemia (AML) remains unknown. The current study was intended to investigate the clinical significance of GPX3 promoter methylation in de novo AML patients and further determine its role in regulating GPX3 expression. GPX3 promoter methylation status was detected in 181 de novo AML patients and 44 normal controls by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. Real-time quantitative PCR was carried out to assess GPX3 expression. GPX3 promoter was significantly methylated in AML patients compared with normal controls (P=0.022). The patients with GPX3 methylation presented significantly older age than those with GPX3 unmethylation (P=0.011). GPX3 methylated patients had significantly lower frequency of C/EBPA mutation and higher incidence of FLT3-ITD mutation (P=0.037 and 0.030, respectively). The non-M3 patients with GPX3 methylation had significantly lower overall survival than those with GPX3 unmethylation (P=0.036). No significant correlation was observed between GPX3 expression and its promoter methylation (R=0.110, P=0.284). However, GPX3 mRNA level was significantly increased after 5-aza-2’-deoxycytidine treatment in leukemic cell line THP1. Our data suggest that GPX3 methylation predicts adverse clinical outcome in non-M3 AML patients. Moreover, GPX3 expression is regulated by its promoter methylation in leukemic cell line THP1. 相似文献
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GPX3 hypermethylation serves as an independent prognostic biomarker in non-M3 acute myeloid leukemia
Jing-Dong Zhou Dong-Ming Yao Ying-Ying Zhang Ji-Chun Ma Xiang-Mei Wen Jing Yang Hong Guo Qin Chen Jiang Lin Jun Qian 《American journal of cancer research》2015,5(5):1786-1794
Hypermethylation of GPX3 (glutathione peroxidase 3) promoter has been identified in various solid tumors. However, the pattern of GPX3 promoter methylation in acute myeloid leukemia (AML) remains poorly known. The current study was intended to investigate the clinical significance of GPX3 promoter methylation in de novo AML patients and further determine its role in regulating GPX3 expression. GPX3 promoter methylation status in 181 de novo AML patients and 44 normal controls was detected by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR. Real-time quantitative PCR was carried out to assess GPX3 expression. GPX3 promoter was significantly methylated in 181 AML patients compared with normal controls (P=0.022). The patients with GPX3 methylation presented significantly older age than those with GPX3 unmethylation (P=0.011). GPX3 methylated patients had significantly lower frequency of C/EBPA mutation and higher incidence of FLT3-ITD mutation (P=0.037 and 0.030). The non-M3 patients with GPX3 methylation had significantly lower overall survival than thoes with GPX3 unmethylation (P=0.036). No significant correlation was observed between GPX3 expression and its promoter methylation (R=0.110, P=0.284). However, GPX3 mRNA level was significantly increased after 5-aza-2’-deoxycytidine treatment in leukemic cell line THP1. GPX3 methylation predicts adverse clinical outcome in non-M3 AML patients. Moreover, GPX3 expression is regulated by its promoter methylation in leukemic cell line THP1. 相似文献
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Noriyoshi Iriyama Yoshihiro Hatta Jin Takeuchi Yoshiaki Ogawa Shigeki Ohtake Toru Sakura Kinuko Mitani Fumihiro Ishida Masatomo Takahashi Tomoya Maeda Tohru Izumi Hisashi Sakamaki Shuichi Miyawaki Sumihisa Honda Yasushi Miyazaki Tomohiko Taki Masafumi Taniwaki Tomoki Naoe 《Leukemia research》2013
We investigated the significance of surface antigen expression for prognosis by focusing on a specific subtype, AML with t(8;21). The investigation included 144 patients with AML with t(8;21) in the JALSG AML97 study. AML with t(8;21) expressed CD19 (36%), CD34 (96%), and CD56 (65%) more frequently than did other subtypes of AML. CD19 expression had a significant favorable effect on CR (95.7% vs. 83.8%; P = 0.049). Univariate analysis showed that increased white blood cell (WBC) counts (WBC ≥ 20 × 109/L), CD19 negativity, and CD56 positivity were critical adverse factors for relapse after CR; multivariate analysis revealed that WBC count and CD56 expression were independent adverse risk factors (HR 2.18; P = 0.045, HR 2.30; P = 0.011, respectively). We concluded that CD56 expression has a possible role in risk stratification for patients with AML with t(8;21). 相似文献
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Yun Li Jiang Lin Jing Yang Jun Qian Wei Qian Dong-ming Yao Zhao-qun Deng Qing Liu Xing-xing Chen Dong Xie Cui An Chun-yan Tang 《Leukemia research》2013
Dysregulation of microRNA let-7a-3 has been identified in several solid tumors and is associated with prognosis of patients. However, the pattern of let-7a-3 expression and the impact on prognosis has not yet been studied in acute myeloid leukemia (AML). The purpose of this study is to investigate the expression status of let-7a-3 and its clinical significance in AML patients using real-time quantitative PCR. Overexpression of let-7a-3 was identified in 25 of 102 (25%) de novo AML. There was no significant difference in age, blood parameters, FAB/WHO subtypes, karyotype risks and nine gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3A, C/EBPA and N/K-RAS) between patients with and without let-7a-3 overexpression (P > 0.05). The patients with let-7a-3 overexpression had similar rates of complete remission (CR) as those without let-7a-3 overexpression (50% vs. 56%, P = 0.693). Although the overall survival (OS) of AML patients with let-7a-3 overexpression (median 12 months,) was shorter than those without overexpression (median 25 months), the difference was not statistically significant (P = 0.228). However, among those 51 obtained CR, patients with let-7a-3 overexpression had significantly shorter OS than those without let-7a-3 overexpression (P = 0.029). The difference in relapse-free survival (RFS) was also significant between two groups (P = 0.005). These findings suggest that let-7a-3 overexpression is a common event and is associated with poor clinical outcome in AML. 相似文献
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Mueller S Phillips J Onar-Thomas A Romero E Zheng S Wiencke JK McBride SM Cowdrey C Prados MD Weiss WA Berger MS Gupta N Haas-Kogan DA 《Neuro-oncology》2012,14(9):1146-1152
The signaling pathways that underlie the pathogenesis of pediatric gliomas are poorly understood. We characterized the PI3K/Akt/mTOR pathway in pediatric gliomas of all grades. Using immunohistochemistry, we assessed activation of the PI3K/Akt/mTOR pathway by evaluating the downstream signaling molecules phospho(p)-S6, phospho(p)-4BP1, and phospho(p)-PRAS40; PTEN; and PTEN promoter methylation, as well as the MIB labeling index. We correlated these findings with the clinical outcomes of 48 children with gliomas. Eighty percent of high-grade gliomas (12/15) showed activation of the PI3K/Akt/mTOR pathway based on p-S6 and p-4EBP1 expression. The majority of high-grade gliomas were negative for PTEN expression (10/15), and 50% had PTEN promoter methylation (grade III: 2/4; grade IV: 3/6). Low-grade gliomas demonstrated PI3K/Akt/mTOR pathway activation in 14/32 (43.8%) by p-S6 and 16/32 (50%) by p-4EBP1. Over 50% of grade I (6/11) and almost all grade II tumors (6/7) showed PTEN promoter methylation. Tumor grade correlated negatively with PTEN expression and positively with expression of p-S6 and p-4EBP1 (PTEN: P = .0025; pS6: P = .0075; p-4EBP1: P = .0066). There was a trend toward inverse correlation of methylation of the PTEN promoter with expression of PTEN protein (P= .0990) and direct correlation of expression of p-S6 and p-4EBP1 with poorer clinical outcome, as measured by progression-free survival (p-S6: P= .0874; p-4EBP1: P= .0475). Tumors with no PTEN expression had a higher MIB labeling index (P= .007). The majority of pediatric gliomas show activation of the PI3K/Akt/mTOR pathway, with methylation of the PTEN promoter occurring commonly in these tumors. 相似文献
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Yu-Jing Zhang Haiyang Li Hui-Chen Wu Jing Shen Lin Wang Ming-Whei Yu Po-Huang Lee I. Bernard Weinstein Regina M. Santella 《Cancer letters》2009
The Hint1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. Previous studies in mice provided evidence that Hint1 may be haploinsufficient with respect to its function as a tumor suppressor. In the present study, we investigated the aberrant methylation of Hint1 and explored possible relationships between aberrant methylation and clinicopathological features in hepatocellular carcinoma (HCC). Hypermethylation of Hint1 was evaluated by the methylation specific PCR (MSP) method in 40 patients with HCC (tumor and paired adjacent non-tumor tissues) from Taiwan, 22 cases of normal liver tissue (14 from Taiwan and 8 from the US). HINT1 expression in tissues was detected by immunohistochemistry. The frequencies of hypermethylation of Hint1 in tumor, paired adjacent non-tumor and normal liver tissue were 55.0%, 37.5% and 9.1%, respectively. A statistically significant inverse association was found between Hint1 methylation status and expression of the HINT1 protein in tumor tissues (p = 0.003). The relationship between Hint1 methylation status and clinical features and other, previously measured biomarkers was also analyzed. p16 hypermethylation was statistically significantly associated with Hint1 methylation status (p = 0.035). There were no correlations between Hint1 methylation and hepatitis B (HBV) or hepatitis C (HCV) infection status or aflatoxin B1 (AFB1-) and polycyclic aromatic hydrocarbons (PAHs)-DNA adduct levels. These results suggest that promoter hypermethylation of Hint1 may play a role in hepatocarcinogenesis. 相似文献
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The CpG island hypermethylation of the suppressor of cytokine signaling-1 (SOCS-1) gene is frequently methylated in hepatocellular carcinoma (HCC), but its clinicopathological significance and the potential risk factors for the epigenetic change in HCC remain poorly understood. The methylation status of SOCS-1 CpG island was evaluated in fresh-frozen tissues from 284 HCC patients using the methylation-specific polymerase chain reaction. The expression of SOCS-1 protein was analyzed by immunohistochemical staining. SOCS-1 methylation was found in 163 (57%) of 284 HCCs. SOCS-1 methylation was positively associated with patient age (P = 0.002) and HCV infection status (P = 0.004), and was inversely associated with HBV infection (P = 0.0002). In the multivariate logistic regression analysis, the HBsAg-negative HCCs showed a 2.78 (95% CI = 1.31–5.89, P = 0.007) times greater risk of SOCS-1 methylation than the HBsAg-positive HCCs. SOCS-1 methylation also occurred at a 4.34 times (95% CI = 1.24–14.25, P = 0.02) higher prevalence in antiHCV-positive cases than in antiHCV-negative cases. No prognostic effect of SOCS-1 methylation was observed in the HCCs. In conclusion, the present study suggests that SOCS-1 methylation in HCC may be negatively associated with HBsAg status. 相似文献
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Purpose
To investigate whether methylation of BRMS1 is associated with clinical outcomes in patients with NSCLC.Methods
Methylation status of BRMS1 was examined in 325 NSCLC patients who were treated with surgery. We analyzed associations between the methylation of BRMS1 genes separately and available epidemiologic and clinical information including smoking status, gender, age, and histological type, or the stage of the tumor.Results
In the cohort of 325 NSCLC cases, 152 samples were identified as methylated (46.77%). Promoter methylation of BRMS1 was present only in 6 specimens (8.42%) in adjacent non-cancerous tissues (P = 2.257 × 10−14). Patient smoking history had a positive correlation with methylation rate of BRMS1 (OR = 2.508, 95%CI(1.516, 4.151)). Compared with unmethylated group, methylated group showed the lower level of BRMS1 mRNA (P = 0.013). And patients with a high level of BRMS1 mRNA expression had significantly better overall survival than those with low expression (P = 0.002). Multivariate Cox proportional hazard regression analysis also showed that promoter methylation of BRMS1 was significantly unfavorable prognostic factors (hazard ratio, 1.912; 95% CI, and 1.341-2.726).Conclusions
These results provide clinical evidence to support the notion that BRMS1 is a NSCLC metastasis suppressor gene. Measuring methylation status of BRMS1 promotor is a useful marker for identifying NSCLC patients with worse disease-free survival. 相似文献15.
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Antonio R. Lucena-AraujoFabio Morato de Oliveira Sabrina Dias Leite-CuevaGuilherme Augusto dos Santos Roberto Passeto FalcaoEduardo Magalhães Rego 《Leukemia research》2011,35(2):260-264
In the present study, we analyzed AURKA and AURKB gene expression in 70 acute myeloid leukemia (AML) patients. There was no difference between leukemic samples and bone marrow mononuclear cells (BMMCs, n = 8) or CD34+ progenitors (n = 10) from healthy donors. High white blood cells (WBC) counts were observed in the AURKA+ and AURKB+ groups, but no significant differences regarding age, gender, platelet counts or frequency of FLT3-ITD mutations. AURKA, but not AURKB, expression was independently associated with high WBC counts (OR: 3.15, 95%CI 1.07-9.24, p = 0.03). Moreover, the majority of cases that overexpressed AURKA and AURKB presented unfavorable cytogenetic abnormalities (p < 0.001). In conclusion, we described a significant association between overexpression of AURKA/B and cytogenetics findings in AML, which may be relevant to new therapeutic approaches, based on Aurora kinase inhibitors. 相似文献
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Xavier Calvo Meritxell Nomdedeu Alfons Navarro Rut Tejero Dolors Costa Concha Muñoz Arturo Pereira Oscar Peña Ruth M. Risueño Mariano Monzó Jordi Esteve Benet Nomdedeu 《Leukemia research》2014
The prognostic impact of global DNA methylation and hydroxymethylation was assessed in 90 patients with de novo myelodysplastic syndrome (MDS). DNA was isolated from bone marrow samples obtained at diagnosis and global methylation and hydroxymethylation were determined by ELISA. Patients with a percentage of methylated DNA above 2.73% had a shorter overall survival than those with lower levels (P = 0.018) and presented a negative trend in terms of leukemia-free survival (P = 0.084), that was statistically significant after censoring 9 patients that received disease-modifying treatments both in univariate and multivariate analyses. Similarly, the low-risk MDS patients defined by the IPSS, WPSS and IPSS-R with 5-mC percentage in total DNA above 2.73% had a shorter overall survival (P = 0.032; P = 0.023; P = 0.031). No cut-off value for the 5-hydroxymethylcytosine percentage with statistical significance for overall or leukemia-free survival was obtained. This study suggests that global DNA methylation predicts overall survival in myelodysplastic syndromes. 相似文献
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Somatic DNA methyl transferase 3A (DNMT3A) mutations have been recognized recently as recurrent molecular aberrations in acute myeloid leukemia (AML). The precise role of these mutations in leukemogenesis remains elusive but a number of studies have already been conducted to study their potential prognostic value in AML patients with variable results. We performed a meta-analysis on published data from over 4500 AML patients to provide robust evidence supporting DNMT3A mutation testing in clinical setting for AML patients. Our meta-analysis showed that DNMT3A mutations were associated with M4 and M5 AML subtypes. Those mutations conferred significantly worse prognosis with both shorter OS (p = 0.0004) and shorter RFS (p = 0.002). Notably, DNMT3A mutations appeared to be an independent adverse prognostic factor also in younger patients with normal cytogenetics AML (OS (p = 0.01) and RFS (p = 0.0005)) and also in the subgroup of patients with high risk genotypes defined according to the criteria of the European Leukemia Net (ELN) (OS (p = 0.002)). Therefore, DNMT3A mutational status can improve the risk stratification of AML patients in the setting of integrated mutational profiling. 相似文献
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Rivero A Rapado I Tomás JF Montalbán C de Oña R Paz-Carreira J Canales M Martínez R Sánchez-Godoy P de Sevilla AF de la Serna J Martínez-López J 《Leukemia research》2011,35(4):431-437
DCK catalyzes the intracellular phosphorylation of fludarabine. The promoter and coding region of the DCK gene were analyzed in 74 follicular lymphoma (FL) patients receiving a therapeutic regimen that included fludarabine. DCK mRNA expression was quantified in a cohort of healthy donors. Four previously described genotypic variants, −360C>G, −201C>T (rs2306744), C28624T (rs11544786) and c.91+37G>C (rs9997790), as well as the new variant, −12C>G, were identified. Variant C28624T showed a lower risk of lymphopenia (P = 0.04), but a higher risk of neutropenia (P = 0.04). Statistical significance was found in bivariate logistic regression between lymphopenia and infectious episodes in the induction period (odds ratio 3.85, P = 0.04). 相似文献
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Ren S Zhou S Wu F Zhang L Li X Zhang J Xu J Lv M Zhang J Zhou C 《Lung cancer (Amsterdam, Netherlands)》2012,75(1):102-109