10 results on '"Qin-Rong Wang"'
Search Results
2. Integrative genomic and transcriptomic profiling reveals distinct molecular subsets in adult mixed phenotype acute leukemia
- Author
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Qian Wang, Wen‐zhi Cai, Qin‐rong Wang, Ming‐qing Zhu, Ling‐zhi Yan, Yan Yu, Xie‐bing Bao, Hong‐jie Shen, Hong Yao, Jun‐dan Xie, Tong‐tong Zhang, Ling Zhang, Xiao‐yu Xu, Zhe Shan, Hong Liu, Jian‐nong Cen, Dan‐dan Liu, Jin‐lan Pan, Da‐ru Lu, Jia Chen, Yang Xu, Ri Zhang, Ying Wang, Sheng‐li Xue, Miao Miao, Yue Han, Xiao‐wen Tang, Hui‐ying Qiu, Ai‐ning Sun, Jin‐yan Huang, Hai‐ping Dai, De‐pei Wu, and Su‐ning Chen
- Subjects
Hematology - Abstract
Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.
- Published
- 2022
3. CagA sequence differences and proteome profiles between East Asian and Western H. pylori strains
- Author
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Lucas Zellmer, Wen-ling Wang, Feng Gin, Qi-Fang Zhang, De-Zhong Liao, Qin-Rong Wang, Lin Xiong, Xinying Quan, Jianjiang Zhou, Yan Zhao, and Yang Xie
- Subjects
Genetics ,Proteome ,CagA ,Biology ,bacterial infections and mycoses ,Sequence (medicine) - Abstract
Background The cytotoxin-associated gene A protein (CagA), an effector protein of Helicobacter pylori (H. pylori), was the first identified bacterium oncoprotein. Based on its sequence characteristics, H. pylori has been classified into East Asian and Western strains. We hypothesized that the differences in structure of CagA and proteomic profiles between East Asian and Western H. pylori strains are the primary cause of the differential clinical outcomes of H. pylori infection. Results In this study, we isolated 27 H. pylori strains from gastric mucosa of Chinese patients with gastric diseases and revealed that the Western CagA has more variation in its EPIYA motifs than East Asian CagA. This result was further confirmed via analyzing the CagA sequences of 150 H. pylori strains from GenBank. More importantly, we detected the deletion or partial deletion of 13 amino acids in CagA in all East Asian strains but not in Western strains. iTRAQ -based proteomic analysis showed that the CagA protein related to cytotoxicity was highly expressed in Western strains, while urease-associated proteins UreA and UreH, flagellin related proteins FlaA, FlgE and FlhA, and cell division proteins FtsZ and FtsI were highly expressed in East Asian strains. These proteins were associated with the colonization, motility, and viability potential of H. pylori in the human stomach and were clustered into an interaction network. Conclusions This study provides significant, unreported differential sequences of CagA and proteomic profiles between East Asian and Western H. pylori, which maybe serves as promising new targets to ascertain the pathogenesis of H. pylori.
- Published
- 2020
4. [Effect of LPXN Overexpression on the Proliferation, Adhesion and Invasion of THP-1 Cells and Its Mechamisms]
- Author
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Hai-Ping, Dai, Guo-Hua, Zhu, Li-Li, Wu, Qian, Wang, Hong, Yao, Qin-Rong, Wang, Li-Jun, Wen, Hui-Ying, Qiu, Qun, Shen, Su-Ning, Chen, and De-Pei, Wu
- Subjects
Matrix Metalloproteinase 9 ,THP-1 Cells ,Cell Line, Tumor ,Cell Adhesion ,Humans ,Matrix Metalloproteinase 2 ,Phosphoproteins ,Cell Adhesion Molecules ,Cell Proliferation - Abstract
To explore the effect of LPXN overexpression on the proliferation, adhesion and invasion of THP-1 cells and its possible mechanism.A THP-1 cell line with stable overexpression of LPXN was constucted by using a lentivirus method, CCK-8 was used to detect the proliferation of cells, adhesion test was used to evaluate adhesion ablity of cells to Fn. Transwell assay was used to detect the change of invasion capability. Western blot was used to detect expression of LPXN, ERK, pERK and integrin α4, α5, β1, the Gelatin zymography was applied to detect activity of MMP2/MMP9 secreted by the THP-1 cells.Successful establishment of THP-1 cells with LPXN overexpression (THP-1 LPXN) was confirmed with Western blot. THP-1 LPXN cells were shown to proliferate faster than the control THP-1 vector cells. Adhesion to Fn and expression of ERK, integrin α4, α5 and β1 in the THP-1 LPXN cells were higher than that in the control cells. Invasion across matrigel and enhanced activity of MMP2 could be detected both in the THP-1 LPXN cells as compared with the control cells.Ectopically ovexpression of LPXN may promote proliferation of THP-1 cells through up-regulation of ERK; promote adhesion of THP-1 cells through up-regulating the integrin α4/β1 as well as integrin α5/β1 complex; promote invasion of THP-1 cells through activating MMP2.
- Published
- 2017
5. Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China
- Author
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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
6. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia
- Author
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Xiaojing Yan, Xing Fan, Yang Shen, Sai-Juan Chen, Jing-Yi Shi, Han Yan, Bing Chen, Jie Jin, Chun-Lei Jiang, Qin-Rong Wang, Yong-Mei Zhu, Zhaohui Gu, Zhu Chen, Feifei Chen, Hai-Min Chen, and Yan-Yan Wang
- Subjects
Adult ,Genetic Markers ,Male ,NPM1 ,Myeloid ,Adolescent ,Oncogene Proteins, Fusion ,Immunology ,Gene mutation ,Biology ,medicine.disease_cause ,Biochemistry ,DNA Methyltransferase 3A ,Cohort Studies ,Young Adult ,Predictive Value of Tests ,hemic and lymphatic diseases ,CEBPA ,medicine ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,Genetic Testing ,Aged ,Genetic testing ,Aged, 80 and over ,Mutation ,medicine.diagnostic_test ,Gene Expression Regulation, Leukemic ,Gene Expression Profiling ,Myeloid leukemia ,Cell Biology ,Hematology ,DNA Methylation ,Middle Aged ,Prognosis ,medicine.disease ,Neoplasm Proteins ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Drug Resistance, Neoplasm ,Cancer research ,Female ,Nucleophosmin - Abstract
To evaluate the prognostic value of genetic mutations for acute myeloid leukemia (AML) patients, we examined the gene status for both fusion products such as AML1 (CBFα)–ETO, CBFβ-MYH11, PML-RARα, and MLL rearrangement as a result of chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS, NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients. Clinical analysis was mainly carried out among 605 cases without recognizable karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were found to have at least 1 mutation, and the relationship of gene mutations with clinical outcome was investigated. We revealed a correlation pattern among NPM1, DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis identified DNMT3A and MLL mutations as independent factors predicting inferior overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and EFS in both the whole group and among younger patients < 60 years of age. The use of molecular markers allowed us to subdivide the series of 605 patients into distinct prognostic groups with potential clinical relevance.
- Published
- 2011
7. [Clinical and laboratorial analysis for 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or positive BCR-ABL]
- Author
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Ling-Zhi, Yan, Su-Ning, Chen, Na-Na, Ping, Qin-Rong, Wang, Hong, Liu, Zi-Xuan, Ding, Ming-Qing, Zhu, Jian-Ying, Liang, Dan-Dan, Liu, Jian-Nong, Cen, Jin-Lan, Pan, Hui-Ying, Qiu, Ai-Ning, Sun, and De-Pei, Wu
- Subjects
Adult ,Aged, 80 and over ,Male ,Adolescent ,Fusion Proteins, bcr-abl ,Hematopoietic Stem Cell Transplantation ,Antigens, CD34 ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Survival Rate ,Young Adult ,Phenotype ,Karyotyping ,Humans ,Female ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies - Abstract
The purpose of this study was to summary the clinical and laboratorial features in 15 adult cases of mixed phenotypic acute leukemia with Ph chromosome and/or BCR-ABL fusion gene positive (Ph(+)MPAL), 15 adult patients with Ph(+)MPAL were defined by WHO-2008 classification. The clinical characteristics, results of morphology, immunology, cytogenetics and molecular genetic detections and results of follow-up in 15 adult patients with Ph(+)MPAL were analyzed retrospectively. The results showed that 15 patients among 87 cases of MPAL demonstrated Ph(+)MPAL (17.2%; 15/87) (7 males and 8 females), their median age was 51 (range 16-81) year old and median WBC count at diagnosis was 69 (12.7-921)×10(9)/L. Based on FAB criteria, these patients showed different morphologic types, including AML (13.3%; 2/15), ALL (40.0%; 6/15), HAL (46.7%; 7/15). Immunologic analysis indicated that 15 cases of Ph(-)MPAL were all classified as B-lymphoid +myeloid mixed immunophenotype. Except one patient, all expressed CD34 antigen on the surface of leukemia cells with 64.3% strong positive, only Ph (53.3%; 8/15), Ph with additional chromosomal abnormalities (33.3%; 5/15) and normal karyotype (13.3%; 2/15) were cytogenetically identified. BCR-ABL fusion gene transcript positive were detected by multiplex reverse transcription PCR in all cases, with e1a2 subtype (p190) (40.0%; 6/15) and b2a2 or b3a2 (p210) subtype (60.0%; 9/15). Four out of 7 (57.1%) patients were found to have IKZF1 gene deletion, without other common gene mutations. Seven out of 10 cases (70.0%) achieved complete remission (CR) after one cycle of induction chemotherapy. In the induction stage, CR rate seemed higher when tyrosine kinase inhibitors (TKI) were added to chemotherapy (83.3%:50.0%; P = 0.206). Overall survival (OS) in 4 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was longer than that in 4 patients received chemotherapy alone (P = 0.004). It is concluded that Ph(+)MPAL mainly is expressed as B+My phenotype. The majority of patients is older and has CD34 overexpression. In the aspect of molecular genetics, the Ph(+)MPAL is similar to other acute leukemia with Ph chromosome. Ph(+)MPAL is a subtype of acute leukemia with poor prognosis. WBC count at diagnosis is an independent prognostic factor. The combination of TKI and allo-HSCT can improve their long-term survival, which needs to be confirmed through carrying out a prospective and multicenter clinical trial for newly diagnosed Ph(+)MPAL.
- Published
- 2013
8. Clinical and experimental characteristics of 20 patients with acute myeloid leukemia with complex variant of t(821)
- Author
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Jing, Xia, Su-Ning, Chen, Jin-Lan, Pan, Qin-Rong, Wang, Ya-Fang, Wu, Yong, Wang, Jun, Zhang, Juan, Shen, Yong-Quan, Xue, and Chang-Geng, Ruan
- Subjects
Adult ,Male ,Adolescent ,Chromosomes, Human, Pair 21 ,DNA Mutational Analysis ,Middle Aged ,Protein-Tyrosine Kinases ,Translocation, Genetic ,Leukemia, Myeloid, Acute ,Young Adult ,Humans ,Female ,Aged ,Chromosomes, Human, Pair 8 ,Retrospective Studies - Abstract
This study was aimed to summarize and analyze the morphology, immunophenotype, cytogenetics, molecular biology (MICM), tyrosine kinase (TK) gene mutations and clinical features of acute myeloid leukemia (AML) with complex variant of t(8;21). A retrospective study was performed for 20 AML patients with complex variant of t(8;21) in our hospital from January 1994 to April 2012, including analysis of clinical feature, immunophenotype, chromosome karyotype, treatment regimen, as well as the overall survival (OS) and relapse-free survival (RFS). Mutations of C-KIT, FLT3-ITD, FLT3-TKD and JAK2V617F were detected by genomic DNA PCR and the sequencing was per-formed in 13 AML patients with complex variant of t(8;21). The results showed that (1) the incidence of 20 AML patients with complex variant of t(8; 21) was 2.4% of total t(8; 21) AML patients. In 20 AML patients with complex variant of t(8;21), 1 case was M1, 17 cases were M2, 2 cases were M4; 10 cases were myeloid phenotype and the other 3 were myeloid plus lymphoid phenotype. There were 16 kinds of cytogenetics additional involvement of chromosomal breakpoints: lp22, 1p32, 2q35, 2q14, 3p25, 5q13, 6p22, 7q21, llq11, 1lq13, 12q14, 12q24, 12p12, 14q32, 15p13, 20q12. (2) C-KIT aberrations were detected in 30.8% cases, all mutated in exon 17 (mutkit 17), only 1 case had JAK2V617F mutation. The result of FLT3 mutation screenings in AML patients with complex variant of t(8; 21) was negative. Of 5 patients with gene mutations, 1 patient (20%) achieved complete remission (CR), the median RFS and median OS time were 6.5 months and 8.9 months respectively. Of the 8 patients without gene mutations, 6 patietns (75%) achieved CR; the median RFS and median OS time were 26.6 months and 27.7 months respectively. It is concluded that the AML patients with complex variant of t(8;21) shows typical features of t(8;21) AML, but the existence of the tyrosine kinase-related gene mutation has important implications on remission rate and long-term survival of patients treated by induction chemotherapy.
- Published
- 2013
9. [Mutational detection of full-length mixed lineage leukemia gene in patients with de novo AML-M4 and M5]
- Author
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Qin-Rong, Wang, Jing-Yi, Shi, Lin, Shi, and Sai-Juan, Chen
- Subjects
Alternative Splicing ,Base Sequence ,Oncogene Proteins, Fusion ,Chromosomes, Human, Pair 11 ,DNA Mutational Analysis ,Leukemia, Monocytic, Acute ,Molecular Sequence Data ,Mutation ,Humans ,Histone-Lysine N-Methyltransferase ,Leukemia, Myelomonocytic, Acute ,Myeloid-Lymphoid Leukemia Protein - Abstract
Abnormalities of chromosome 11 involving mixed lineage leukemia (MLL) on 11q23 are often seen in acute myeloid leukemia (AML)-M5 or AML-M4. The fusion gene of MLL-PTD and MLL plays a critical role in the pathogenesis of these AML. However, rare chromosome abnormalities have been identified in this type of leukemia. To explore whether there were other MLL gene mutations at M4 and M5, in this study all of the MLL exons were sequenced at cDNA level. 25 patients with de novo AML-M4 or M5 with normal karyotypes excluding M4eo and MLL fusion gene or MLL-PTD were selected, the amplification and direct sequencing analysis of full length MLL gene exons were carried out, then the mutations found were verified at genomic DNA level. Furthermore, the point mutations were tested in normal samples and a larger group of AML patients using the platform of Mass Array. The results showed that high-frequency deletion/insertion and point mutations in RD, PHD, TAD and SET domains of MLL were found, while these alterations in normal samples and other subtypes of AML samples were also verified, and without significant difference (P0.05). It is concluded that a variety of deletions/insertions in MLL mRNA and point mutations are respectively alternative splicing of MLL gene at transcriptional level and single nucleotide polymorphism. These alternations together constituted genetic polymorphisms of MLL. Although these variations may not play a direct role in the molecular pathogenesis of AML-M4 or M5, their correlations to clinical treatment and prognosis need to be further explored.
- Published
- 2012
10. Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China.
- Author
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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
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