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Your search keyword '"Song-Fang Wu"' showing total 4 results
Start Over Author "Song-Fang Wu" Topic dna methylation
4 results on '"Song-Fang Wu"'

1. Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement

Author

Sai-Juan Chen, Ze-Guang Han, Wei-Na Zhang, Yu-Jun Dai, Ying Yang, Xianbin Su, Yue-Ying Wang, Jinyan Huang, Song-Fang Wu, Li Xia, Xiao-Dong Shi, Jian-Qing Mi, Jie Xu, Jing Lu, Zhu Chen, Ting Huang, and Pan-Pan Wang

Subjects
0301 basic medicine, Myeloid, Cellular differentiation, Biology, DNA Methyltransferase 3A, Transcriptome, Mice, 03 medical and health sciences, hemic and lymphatic diseases, medicine, Animals, DNA (Cytosine-5-)-Methyltransferases, Gene Knock-In Techniques, Progenitor cell, DNA Modification Methylases, PI3K/AKT/mTOR pathway, Multidisciplinary, Base Sequence, Gene Expression Profiling, TOR Serine-Threonine Kinases, Myeloid leukemia, Cell Differentiation, DNA Methylation, Biological Sciences, medicine.disease, Molecular biology, Disease Models, Animal, Leukemia, Myeloid, Acute, Leukemia, 030104 developmental biology, medicine.anatomical_structure, Mutation, embryonic structures, DNA methylation
Abstract

Significance DNMT3A is a critical epigenetic modifier and tumor suppressor in the hematopoietic system. This gene is frequently mutated in hematopoietic malignancies, including acute myeloid leukemia (AML), with Dnmt3a R878H being the most common mutant. By using a conditional knockin approach, this study shows that Dnmt3a R878H is sufficient to initiate AML and recapitulate human leukemic features in mice. The leukemia-initiating cells are enriched in hematopoietic stem/progenitor cells. Through gene expression profiling, DNA methylation and histone modification analysis, and functional tests on important regulators for cell proliferation and differentiation in an animal model, this study has not only discovered mTOR pathway activation as a key player in the disease mechanism but also revealed the potential therapeutic effects of mTOR inhibition on DNMT3A mutation-related leukemia.

Published
2017

2. Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China

Author

Depei Wu, Jin-Song Yan, Yang Shen, He Huang, Wenlian Chen, Bing-Shun Wang, Yunping Qiu, Zhu Chen, Yan Li, Song-Fang Wu, Yong-Mei Zhu, Xiaojing Yan, Wei-Na Zhang, Tianlu Chen, Wei Jia, Qiuling Ma, Jian-Qing Mi, Jiang-Han Wang, Sai-Juan Chen, Jie Jin, Shuai Wang, Jian-Yong Li, Junmin Li, Xiao-Jun Huang, Yang Li, Aihua Zhao, Qin-Rong Wang, and Yungui Wang

Subjects
Multidisciplinary, IDH1, Metabolite, Myeloid leukemia, Biological Sciences, Biology, medicine.disease, IDH2, Lymphoma, chemistry.chemical_compound, Isocitrate dehydrogenase, chemistry, hemic and lymphatic diseases, DNA methylation, Immunology, Cancer research, medicine, Clinical significance
Abstract

The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an “oncometabolite.” To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph–time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 μg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis.

Published
2013

3. Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement.

Author

Yu-Jun Dai, Yue-Ying Wang, Jin-Yan Huang, Li Xia, Xiao-Dong Shi, Jie Xu, Jing Lu, Xian-Bin Su, Ying Yang, Wei-Na Zhang, Pan-Pan Wang, Song-Fang Wu, Ting Huang, Jian-Qing Mi, Ze-Guang Han, Zhu Chen, and Sai-Juan Chen

Subjects
ACUTE myeloid leukemia, GENETIC mutation, LABORATORY mice, DNA methylation, RNA sequencing, PROGENITOR cells, GENE expression
Abstract

DNMT3A is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot DNMT3A R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged Lin-Sca1+cKit+ cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage. Consistent with leukemic cell accumulation in G2/M phase, CDK1 was up-regulated due to mTOR activation associated with DNA hypomethylation. Overexpressed CDK1-mediated EZH2 phosphorylation resulted in an abnormal trimethylation of H3K27 profile. The mTOR inhibitor rapamycin elicited a significant therapeutic response in Dnmt3aR878H/WT mice. [ABSTRACT FROM AUTHOR]

Published
2017
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4. Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China.

Author

Jiang-Han Wang, Wen-Lian Chen, Jun-Min Li, Song-Fang Wu, Tian-Lu Chen, Yong-Mei Zhu, Wei-Na Zhang, Yang Li, Yun-Ping Qiu, Ai-Hua Zhao, Jian-Qing Mi, Jie Jin, Yun-Gui Wang, Qiu-Ling Ma, He Huang, De-Pei Wu, Qin-Rong Wang, Yan Li, Xiao-Jing Yan, and Jin-Song Yan

Subjects
ACUTE myeloid leukemia, ISOCITRATE dehydrogenase, HEMATOLOGIC malignancies, DNA methylation, GAS chromatography, TIME-of-flight mass spectrometry
Abstract

The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.01, log2-transformed from 4.03 µg/mL). IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but were observed only in 9 of 31 (29%) patients with moderately high 2-HG, suggesting other genetic or biochemical events may exist in causing 2-HG elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of 2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically normal AML (n = 234), high 2-HG represented a negative prognostic factor in both overall survival and event-free survival. Univariate and multivariate analyses confirmed high serum 2-HG as a strong prognostic predictor independent of other clinical and molecular features. We also demonstrated distinct gene-expression/DNA methylation profiles in AML blasts with high 2-HG compared with those with normal ones, supporting a role that 2-HG plays in leukemogenesis. [ABSTRACT FROM AUTHOR]

Published
2013
Full Text
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