CEBPA methylation and mutation in myelodysplastic syndrome

Wen, Xiang‐mei; Hu, Jiabo; Yang, Jing; Qian, Wei; Yao, Dong‐ming; Deng, Zhaoqun; Zhang, Yingying; Zhu, Xiaowen; Guo, Hong; Jiang, Lin; Qian, Jun

doi:10.1007/s12032-015-0605-z

Cited by 28 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All positive samples were confirmed by DNA sequencing. The other gene mutations including NPM1 , C-KIT , DNMT3A , IDH1 , IDH2 , and U2AF1 were also detected by HRMA [ 28 – 33 ], whereas FLT3 -ITD and CEBPA mutations were examined by DNA sequencing (BGI Tech Solutions Co., Shanghai, China) [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia

Zhou

Yao

et al. 2017

Oncotarget

Self Cite

View full text Add to dashboard Cite

The prognostic value of RAS mutations has been systematically investigated in acute myeloid leukemia (AML). However, clinical significance of RAS expressions in AML remains poorly determined. To explore the clinical significance, we analyzed KRAS and NRAS expressions in 143 de novo AML patients by real-time quantitative PCR. KRAS and NRAS expressions were significantly up-regulated in AML patients. KRAS and NRAS mutations were identified in 4% (6/143) and 8% (12/143) of these patients, respectively. However, no significant association was observed between RAS mutations and expressions. High KRAS expression was associated with older age, higher white blood cells, and a tendency of higher platelets, whereas high NRAS expression was only correlated with older age. Complete remission (CR) rate and overall survival of AML patients were adversely affected by KRAS overexpression, but not NRAS overexpression. Multivariate analysis revealed that KRAS acted as an independent prognostic predictor in cytogenetically normal AML (CN-AML). Moreover, the prognostic value of KRAS expression was validated using the published data from Gene Expression Omnibus datasets. In the follow-up patients, KRAS expression rather than NRAS expression in CR time tended to decrease compared to newly diagnosis time, and both KRAS and NRAS expressions were significantly increased when in relapse time. Our findings revealed that RAS overexpression and mutations were common events in AML with potential therapeutic target value. KRAS overexpression independent of RAS mutations conferred an adverse prognosis in CN-AML.

show abstract

Section: Methodsmentioning

confidence: 99%

KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia

Zhou

Yao

et al. 2017

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…High‐resolution melting analysis (HRMA) and DNA sequencing was performed in the detection of IDH1/2 , U2AF1 , SF3B1 , DNMT3A, and CEBPA mutations as reported previously .…”

Section: Methodsmentioning

confidence: 99%

GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome

et al. 2016

Self Cite

View full text Add to dashboard Cite

Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome (MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real‐time quantitative methylation‐specific PCR (RQ‐MSP) and bisulfite sequencing PCR (BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival (OS) time than those with GPX3 unmethylation analyzed with Kaplan–Meier analysis (P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia (sAML) in three follow‐up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS.

show abstract

“…Gene mutations were detected by high-resolution melting analysis (HRMA) and direct DNA sequencing as reported [22][23][24][25][26][27][28][29].…”

Section: Gene Mutation Detectionmentioning

confidence: 99%

Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies

Zhou

Zhang

et al. 2017

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Promoter hypermethylation-mediated inactivation of ID4 plays a crucial role in the development of solid tumours. This study aimed to investigate ID4 methylation and its clinical relevance in myeloid malignancies. ID4 hypermethylation was associated with higher IPSS scores, but was not an independent prognostic biomarker affecting overall survival (OS) in myelodysplastic syndrome (MDS). However, ID4 hypermethylation correlated with shorter OS and leukaemia-free survival (LFS) time and acted as an independent risk factor affecting OS in acute myeloid leukaemia (AML). Moreover, ID4 methylation was significantly decreased in the follow-up paired AML patients who achieved complete remission (CR) after induction therapy. Importantly, ID4 methylation was increased during MDS progression to AML and chronic phase (CP) progression to blast crisis (BC) in chronic myeloid leukaemia (CML). Epigenetic studies showed that ID4 methylation might be one of the mechanisms silencing ID4 expression in myeloid leukaemia. Functional studies in vitro showed that restoration of ID4 expression could inhibit cell proliferation and promote apoptosis in both K562 and HL60 cells. These findings indicate that ID4 acts as a tumour suppressor in myeloid malignancies, and ID4 methylation is a potential biomarker in predicting disease progression and treatment outcome.

show abstract

CEBPA methylation and mutation in myelodysplastic syndrome

Cited by 28 publications

References 39 publications

KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia

KRAS overexpression independent of RAS mutations confers an adverse prognosis in cytogenetically normal acute myeloid leukemia

GPX3 methylation in bone marrow predicts adverse prognosis and leukemia transformation in myelodysplastic syndrome

Epigenetic dysregulation of ID4 predicts disease progression and treatment outcome in myeloid malignancies

Contact Info

Product

Resources

About