36 results on '"Jing, Yi"'
Search Results
2. Therapeutic Repurposing of Brincidofovir in Natural Killer/T-Cell Lymphoma Reveals Potent Induction of Replication Stress, Sting Pathway Activation and Immunogenic Cell Death
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Chan, Jason Yongsheng, primary, Lee, Elizabeth Chun Yong, additional, Chai, Kelila Xin Ye, additional, Lee, Jing Yi, additional, Kannan, Bavani, additional, Lim, Boon Yee, additional, Kok, Jessica Sook-Ting, additional, Li, Zhimei, additional, Loh, Jui Wan, additional, Ko, Tun Kiat, additional, Lim, Kah Suan, additional, Ng, Cedric Chuan-Young, additional, Lim, Kerry, additional, Huang, Dachuan, additional, Lim, Jing Quan, additional, Hazama, Masatoshi, additional, Fukushima, Koji, additional, Teh, Bin Tean, additional, Lim, Soon Thye, additional, and Ong, Choon Kiat, additional
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- 2022
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3. IRF8 and IRF3 cooperatively regulate rapid interferon-β induction in human blood monocytes
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Li, Peng, Wong, Joyce Jing-Yi, Sum, Calvin, Sin, Wei-Xiang, Ng, Kok-Quan, Koh, Mickey B.C., and Chin, Keh-Chuang
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- 2011
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4. Overexpression of B cell–activating factor of TNF family (BAFF) is associated with Helicobacter pylori–independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma
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Kuo, Sung-Hsin, Yeh, Pei-Yen, Chen, Li-Tzong, Wu, Ming-Shiang, Lin, Chung-Wu, Yeh, Kun-Huei, Tzeng, Yi-Shin, Chen, Jing-Yi, Hsu, Ping-Ning, Lin, Jaw-Town, and Cheng, Ann-Lii
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- 2008
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5. Angiogenesis Induced By Aminoacyl-tRNA Synthetase Deficiency Is Dependent on Amino Acid Response (AAR) but Not Unfolded Protein Response (UPR) Pathways
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Zhang, Fan, primary, Chen, Yi, additional, Jin, Yi, additional, Xu, Chun-Hui, additional, Liu, Dian-Jia, additional, Xu, Ai-Ning, additional, Zhang, Yuan-Liang, additional, Xie, Yin-Yin, additional, Shi, Jing-Yi, additional, Wang, Lan, additional, Huang, Qiu-Hua, additional, Chen, Zhu, additional, Chen, Sai-Juan, additional, and Sun, Xiao-Jian, additional
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- 2018
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6. Angiogenesis Induced By Aminoacyl-tRNA Synthetase Deficiency Is Dependent on Amino Acid Response (AAR) but Not Unfolded Protein Response (UPR) Pathways
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Ai-Ning Xu, Xiao-Jian Sun, Lan Wang, Fan Zhang, Yi Jin, Jing-Yi Shi, Yin-Yin Xie, Qiu-Hua Huang, Dian-Jia Liu, Chun-Hui Xu, Yuanliang Zhang, Zhu Chen, Yi Chen, and Sai-Juan Chen
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Gene knockdown ,EIF-2 kinase ,biology ,Kinase ,Immunology ,ATF4 ,Cell Biology ,Hematology ,biology.organism_classification ,Biochemistry ,Phenotype ,Cell biology ,biology.protein ,Unfolded protein response ,EIF2AK3 ,Zebrafish - Abstract
Stress-induced angiogenesis enormously contributes to both normal development and pathogenesis of various diseases including cancer. Among many stress response pathways implicated in regulation of angiogenesis, the amino acid response (AAR) and the unfolded protein response (UPR) pathways are closely interconnected, as they converge on the common target, eIF2α, which is a key regulator of protein translation. Two kinases, namely Gcn2 (Eif2ak4) and Perk (Eif2ak3), are responsible for transducing signals from AAR and UPR, respectively, to phosphorylation of eIF2α. Even though numerous studies have been performed, this close interconnection between AAR and UPR makes it difficult to clearly distinguish different contributions of these two pathways in regulation of angiogenesis. In this study, we generated a zebrafish angiogenic model harboring a loss-of-function mutation of the threonyl-tRNA synthetase (tars) gene. Tars belongs to a family of evolutionarily conserved enzymes, aminoacyl-tRNA synthetases (aaRSs), which control the first step of protein translation through coupling specific amino acids with their cognate tRNAs. Deficiencies of several aaRSs in zebrafish have been shown to cause increased branching of blood vessels, and this angiogenic phenotype has roughly been explained by activation of AAR and UPR; however, it is unclear whether both AAR and UPR are required and to what extent they contribute to this process. To address this issue, we first performed RNA-seq analyses of Tars-mutated and control zebrafish embryos, as well as those with knockdown of either Gcn2 or Perk in both genotypes. We found that the AAR target genes are dramatically activated in the Tars-mutants, whereas the genes associated with the three UPR sub-pathways (i.e., Perk-, Ire1- and Atf6-mediated pathways) remain inactive, except for very few genes (e.g., Atf3, Atf4, Asns and Igfbp1) that are shared in both AAR and UPR, thus suggesting activation of AAR, but not UPR, in the Tars-mutants. In support of this notion, knockdown of the AAR-associated kinase Gcn2 in the Tars-mutants largely represses the activated genes, while the Perk knockdown shows very little effect. Nonetheless, in contrast to the apparently dispensable role of Perk in Tars-mutants, knockdown of Perk in control embryos leads to specific gene expression alterations, suggesting that Perk effectively functions in homeostatic states (i.e., controls), but, in the stress condition (i.e., Tars-mutants), its function is largely overwhelmed by activation of the Gcn2-mediated AAR. To validate these observations, we investigated the angiogenic phenotypes of the zebrafish models upon genetic and pharmacological interference with the AAR and UPR pathways. A transgenic zebrafish line, Tg(flk1:EGFP), was crossed with the Tars-mutants to visualize angiogenesis in vivo. We observed increased branching of blood vessels in the Tars-mutants, which is rescued by tars mRNA but not an enzymatically dead version. Importantly, knockdown of Gcn2 in the Tars-mutants rescues this phenotype. In contrast, knockdown of Perk, or knockdown of two other known eIF2α kinases, Hri (Eif2ak1) or Pkr (Eif2ak2), shows no effect. Furthermore, knockdown of either one of two major factors downstream to eIF2α, namely Atf4 and Vegfα, or inhibition of Vegf receptor with the drug SU5416, also rescue the phenotype. Thus, these results confirm that AAR, but not UPR, is required for the Tars-deficiency-induced angiogenesis. Taken together, this study demonstrates that, despite being closely interconnected and even sharing a common downstream target, the Gcn2-mediated AAR and the Perk-mediated UPR can be activated independently in different conditions and differentially regulate cellular functions such as angiogenesis. This notion reflects the specificity and efficiency of multiple stress response pathways that are evolved integrally to benefit the organism by ensuring sensing and responding precisely to different types of stresses. This study also provides an example of combining systematic gene expression profiling and phenotypic validations to distinguish activities of such interconnected pathways. Further clarification of the mechanisms shall advance our understanding of how the organisms respond to diverse stresses and how the abnormalities in these regulatory machineries cause cellular stress-related diseases such as cancer, diabetes and immune disorders. Disclosures No relevant conflicts of interest to declare.
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- 2018
7. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia
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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
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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.
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- 2011
8. IRF8 and IRF3 cooperatively regulate rapid interferon-β induction in human blood monocytes
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Wei-Xiang Sin, Joyce Jing-Yi Wong, Mickey Koh, Calvin Sum, Peng Li, Keh-Chuang Chin, and Kok-Quan Ng
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Transcription, Genetic ,Blotting, Western ,Molecular Sequence Data ,Immunology ,Gene Expression ,Electrophoretic Mobility Shift Assay ,Biology ,Biochemistry ,Monocytes ,Mice ,Transcription (biology) ,Proto-Oncogene Proteins ,medicine ,Animals ,Humans ,Immunoprecipitation ,Electrophoretic mobility shift assay ,Promoter Regions, Genetic ,Transcription factor ,Oligonucleotide Array Sequence Analysis ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Monocyte ,Promoter ,Interferon-beta ,Cell Biology ,Hematology ,Flow Cytometry ,Cell biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Interferon Regulatory Factors ,Trans-Activators ,Interferon Regulatory Factor-3 ,IRF8 ,IRF3 ,Interferon regulatory factors - Abstract
Robust and rapid induction of interferon-β (IFN-β) in monocytes after pathogenic stimulation is a hallmark of innate immune responses. Here, we reveal the molecular mechanism underlying this key property that is exclusive to human blood monocytes. We found that IFN-β was produced rapidly in primary human monocytes as a result of cooperation between the myeloid-specific transcription factor IRF8 and the ubiquitous transcription factor IRF3. Knockdown of IRF8 in monocytes abrogated IFN-β transcription, whereas reintroduction of IRF8 into the IRF8−/− 32Dcl3 murine myeloid cell line reinstated IFN-β transcription. Moreover, we provide evidence that IRF8 constitutively binds to the ETS/IRF composite element of the IFN-β promoter region together with PU.1 in vivo. Furthermore we uncovered a requirement for IRF3, a master regulator of IFN-β production, as a previously un-indentified interaction partner of IRF8. We mapped the protein-protein interacting regions of IRF3 and IRF8, and found that their interaction was independent of the DNA-binding domain and the IRF association domain of IRF8 and IRF3, respectively. Therefore, we propose a model for the rapid induction of IFN-β in monocytes, whereby IRF8 and PU.1 form a scaffold complex on the IFN-β promoter to facilitate the recruitment of IRF3, thus enabling rapid IFN-β transcription.
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- 2011
9. Enhancement of Mitochondrial Membrane Potential and Pro-Survival Pathways with Azole Compound C7 Resulting in Expansion of Hematopoietic Stem and Progenitor Cells
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Liu, Kelvin YH, Kok, Ze Hui, Rajasegaran, Vikneswari, Lim, Samantha PS, Jaafar, Muhammad Taufiq, Ouyang, John, Loh, Jui Wan, Lee, Jing Yi, Lim, Abner H, Ng, Cedric Chuan Young, Chan, Jason Yongsheng, Chuah, Charles, Teh, Bin Tean, Bari, Sudipto, and Hwang, William Ying Khee
- Abstract
Ex-vivo expansion of hematopoietic stem & progenitor cells (HSPC) could improve hematopoietic recovery and reduce post-transplant complications, especially for umbilical cord blood (UCB) grafts where limited total cell numbers result in delayed engraftment.
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- 2023
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10. Targeted Integration of a Chimeric Antigen Receptor in Key Selected Loci in Primary Natural Killer Cells
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Allain, Vincent, Rothrock, Allison, Nyberg, William, Muldoon, Joseph, To, Angela, Chung, Jing-Yi, Chang, Christopher, Talbot, Alexis, and Eyquem, Justin
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Despite promising preclinical studies and early clinical data (Liu et al., NEJM, 2020), chimeric antigen receptor natural killer cells (CAR NK) are not yet on par with CAR T cells for the treatment of malignant diseases. Much effort has gone into developing NK-optimized CAR architectures (Li et al., Cell Stem Cell, 2018) and to increasing the persistence of CAR NK cells. We hypothesized that CAR NK cells could also benefit from the targeted integration of a CAR transgene, as compared with semi-random integration obtained using gammaretroviral vectors. Precise targeting has proven highly advantageous for TRACCAR T cells owing to the optimal regulation and homogeneous expression conferred by the endogenous TCR alpha promoter (Eyquem et al., Nature, 2017).
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- 2023
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11. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets
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Hao Han, Kok Loon Wong, Xiaohui Sem, Wei Hseun Yeap, Wing-Cheong Wong, Philippe Kourilsky, June Jing Yi Tai, and Siew Cheng Wong
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medicine.medical_treatment ,CD14 ,Immunology ,Cell Separation ,CD16 ,Biology ,Validation Studies as Topic ,Biochemistry ,Models, Biological ,Monocytes ,Flow cytometry ,medicine ,Cluster Analysis ,Humans ,Gene ,medicine.diagnostic_test ,Microarray analysis techniques ,Monocyte ,Gene Expression Profiling ,Cell Differentiation ,Cell Biology ,Hematology ,Flow Cytometry ,Microarray Analysis ,Cell biology ,Gene expression profiling ,Cytokine ,medicine.anatomical_structure - Abstract
New official nomenclature subdivides human monocytes into 3 subsets: the classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes. This introduces new challenges, as monocyte heterogeneity is mostly understood based on 2 subsets, the CD16− and CD16+ monocytes. Here, we comprehensively defined the 3 circulating human monocyte subsets using microarray, flow cytometry, and cytokine production analysis. We find that intermediate monocytes expressed a large majority (87%) of genes and surface proteins at levels between classical and nonclassical monocytes. This establishes their intermediary nature at the molecular level. We unveil the close relationship between the intermediate and nonclassic monocytes, along with features that separate them. Intermediate monocytes expressed highest levels of major histocompatibility complex class II, GFRα2 and CLEC10A, whereas nonclassic monocytes were distinguished by cytoskeleton rearrangement genes, inflammatory cytokine production, and CD294 and Siglec10 surface expression. In addition, we identify new features for classic monocytes, including AP-1 transcription factor genes, CLEC4D and IL-13Rα1 surface expression. We also find circumstantial evidence supporting the developmental relationship between the 3 subsets, including gradual changes in maturation genes and surface markers. By comprehensively defining the 3 monocyte subsets during healthy conditions, we facilitate target identification and detailed analyses of aberrations that may occur to monocyte subsets during diseases.
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- 2011
12. Exome Sequencing Identifies Somatic Mutations of DDX3X in Natural Killer/T-Cell Lymphoma
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Jiang, Lu, primary, Gu, Zhao-Hui, additional, Yan, Zi-Xun, additional, Zhao, Xia, additional, Xie, Yin-Yin, additional, Zhang, Zi-Guan, additional, Pan, Chun-Ming, additional, Hu, Yuan, additional, Cai, Chang-Ping, additional, Dong, Ying, additional, Wang, Li, additional, Shen, Yang, additional, Meng, Guoyu, additional, Zhou, Jian-Feng, additional, Hu, Jian-Da, additional, Wang, Jin-Fen, additional, Yang, Lin-Hua, additional, Zhang, Feng, additional, Wang, Jian-Min, additional, Wang, Zhao, additional, Peng, Zhi-Gang, additional, Chen, Fang-Yuan, additional, Sun, Zi-Min, additional, Ding, Hao, additional, Huang, Jin-Yan, additional, Liu, Yuan-Hua, additional, Shi, Jumei, additional, Hou, Jian, additional, Yan, Jin-Song, additional, Shi, Jing-Yi, additional, Xu, Lan, additional, Li, Yang, additional, Lu, Jing, additional, Zheng, Zhong, additional, Xue, Wen, additional, Zhao, Wei-Li, additional, Chen, Zhu, additional, and Chen, Sai-Juan, additional
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- 2014
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13. Genome-Wide Abnormality Patterns of B-Lineage Acute Lymphoblastic Leukemia in Adults in Comparison with Pediatric Cases
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Wang, Bai-Yan, primary, Liu, Yuan-Fang, additional, Tang, Jing-Yan, additional, Gu, Zhao-Hui, additional, Zhang, Wei-Na, additional, Zhang, Zi-Guan, additional, Wang, Qiang, additional, Chen, Bing, additional, Wang, Sheng-Yue, additional, Zhu, Yong-Mei, additional, Li, Jun-Min, additional, Wang, Jin, additional, Bai, Yun, additional, Lu, Gang, additional, Yang, Min-Jun, additional, Zhang, Jin-Li, additional, Shi, Jing-Yi, additional, Wang, Kan-Kan, additional, Pan, Chun-Ming, additional, Lu, Jing, additional, Jiang, Lu, additional, Li, Yang, additional, Zhao, Chun-Jun, additional, Chen, Jing, additional, Gu, Long-Jun, additional, Mi, Jian-Qing, additional, Li, Ben-Shang, additional, Chen, Zhu, additional, and Chen, Sai-Juan, additional
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- 2014
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14. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma
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Jing-Yi Chen, Pei Yen Yeh, Sung-Hsin Kuo, Li-Tzong Chen, Yi-Shin Tzeng, Jaw-Town Lin, Ming-Shiang Wu, Chung-Wu Lin, Ann-Lii Cheng, Kun-Huei Yeh, and Ping-Ning Hsu
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Adult ,Male ,Immunology ,Biology ,Biochemistry ,Models, Biological ,immune system diseases ,B-Cell Lymphoma 3 Protein ,Stomach Neoplasms ,hemic and lymphatic diseases ,Cell Line, Tumor ,Proto-Oncogene Proteins ,B-Cell Activating Factor ,medicine ,Humans ,B-cell activating factor ,B cell ,Adaptor Proteins, Signal Transducing ,Aged ,Aged, 80 and over ,Cell Nucleus ,Helicobacter pylori ,NF-kappa B ,MALT lymphoma ,Cell Biology ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Gastric Diffuse Large B-Cell Lymphoma ,Middle Aged ,medicine.disease ,B-Cell CLL-Lymphoma 10 Protein ,BCL10 ,Lymphoma ,Up-Regulation ,Enzyme Activation ,Protein Transport ,medicine.anatomical_structure ,Cancer research ,Female ,Lymphoma, Large B-Cell, Diffuse ,Diffuse large B-cell lymphoma ,Mucosa-associated lymphoid tissue ,Proto-Oncogene Proteins c-akt ,Signal Transduction ,Transcription Factors - Abstract
We have recently demonstrated that nuclear expression of BCL10 predicts Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue (MALT). In this study, we examined the role of B cell–activating factor of TNF family (BAFF) in mediating BCL10 nuclear translocation and HP independence of gastric DLBCL (MALT). We used immunohistochemistry and immunoblotting to measure the expression of BAFF, pAKT, BCL3, BCL10, and NF-κB. Transactivity of NF-κB was measured by electromobility shift assay. In lymphoma samples from 26 patients with gastric DLBCL (MALT), we detected aberrant expression of BAFF in 7 of 10 (70%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015). BAFF overexpression was associated with pAKT expression (P = .032), and nuclear expression of BCL3 (P = .014), BCL10 (P = .015), and NF-κB (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-κB and AKT; the activated NF-κB up-regulated BCL10, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 nuclear translocation, NF-κB transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL (MALT).
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- 2008
15. Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma
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Zhu Chen, Anne Janin, Wei-Li Zhao, Li Wang, José-Francisco Garcia, Yang Shen, Yan-Yan Liu, Junmin Li, Christophe Leboeuf, Jing-Yi Shi, Sai-Juan Chen, and Zhi-Xiang Shen
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Adult ,Male ,Lymphoma, B-Cell ,Adolescent ,Immunology ,Biology ,CHOP ,Biochemistry ,Antibodies, Monoclonal, Murine-Derived ,immune system diseases ,hemic and lymphatic diseases ,Gene expression ,PRDM1 ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,RNA, Messenger ,Cyclophosphamide ,Laser capture microdissection ,Aged ,Retrospective Studies ,Aged, 80 and over ,NF-kappa B ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,Repressor Proteins ,Survival Rate ,Doxorubicin ,Drug Resistance, Neoplasm ,Vincristine ,Monoclonal ,Cancer research ,Prednisone ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,Positive Regulatory Domain I-Binding Factor 1 ,Diffuse large B-cell lymphoma ,medicine.drug ,Transcription Factors - Abstract
The positive regulatory domain I (PRDM1) is a master regulator in the differentiation of mature B lymphocytes to plasma cells. It has 2 isoforms, PRDM1alpha and PRDM1beta, and is regulated by the transcriptional regulator nuclear factor kappa (NF)-kappaB. PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated. Using laser microdissection combined with reverse transcription-polymerase chain reaction (RT-PCR) amplification, PRDM1 gene expression was assessed in 82 DLBCL patients. The results showed that both PRDM1alpha and PRDM1beta transcripts were expressed in microdissected lymphoma cells only in the non-germinal center B-cell-like (non-GCB) subtype of DLBCL. PRDM1beta gene expression was correlated with short survival time in the non-GCB patients treated with CHOP but not with R-CHOP. In vitro, B-lymphoma cells resistant to chemotherapy expressed PRDM1beta. Rituximab suppressed PRDM1beta expression, which was concomitant with NF-kappaB inactivation. The value of PRDM1beta expression as a prognostic marker in non-GCB DLBCL might thus be considered. This study confirms the efficiency of rituximab on DLBCL and allows a better understanding of one of its biologic actions.
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- 2007
16. Genome-Wide Abnormality Patterns of B-Lineage Acute Lymphoblastic Leukemia in Adults in Comparison with Pediatric Cases
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Yuan-Fang Liu, Long-Jun Gu, Bing Chen, Zhu Chen, Zi-Guan Zhang, Sai-Juan Chen, Jin Wang, Shengyue Wang, Jian-Qing Mi, Yong-Mei Zhu, Junmin Li, Jing-Yi Shi, Gang Lu, Jingyan Tang, Kankan Wang, Bai-Yan Wang, Chun-Ming Pan, Zhaohui Gu, Jin-Li Zhang, Minjun Yang, Benshang Li, Wei-Na Zhang, Jing Chen, Yang Li, Qiang Wang, Jing Lu, Yun Bai, Chunjun Zhao, and Lu Jiang
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Genetics ,Immunology ,Cell Biology ,Hematology ,Biology ,Gene mutation ,Bioinformatics ,Biochemistry ,Deep sequencing ,Molecular cytogenetics ,Ion binding ,DNA methylation ,Copy-number variation ,Epigenetics ,Exome sequencing - Abstract
BACKGROUND B-lineage acute lymphoblastic leukemia (B-ALL) represents the most common subtype in ALL. Genomic sequence information has been lacking in adult B-ALL, whose outcome remains dismal, while a comparison between genomic abnormalities in adult and pediatric groups is useful to further decipher disease mechanisms. METHODS We used whole exome sequencing (WES), copy number variation and molecular cytogenetics to catalog somatic mutations in 95 B-ALL patients (43 adults and 52 children).WES was conducted with appropriate depths for paired genomic DNA from bone marrow mononuclear cells at diagnosis and their matched peripheral blood samples during complete remission (CR) or saliva samples. Targeted deep sequencing (TDS) was performed in a validation cohort of 179 adult and 199 pediatric B-ALLs. RESULTS Eighty-four recurrent gene mutations were revealed by WES. Integrative analysis identified the involvement of 9 functional categories of genes: key fusions (KFs), epigenetic modifiers (EMs), signaling molecules (SMs), transcription factors (TFs), tumor suppressors (TSs), actin binding/cytoskeletons (ABCs), ion binding proteins (IBPs), trans-membrane proteins (TPs) and the others. Mutually cooperative or exclusive relationships were revealed among some of these categories. Genomic landscapes suggested two distinct mechanisms involved in the leukemogenesis: one is mainly driven by KFs together with mutations of TFs and TSs; the other results from the abnormalities of TFs and TSs, in cooperation with mutations of EMs, SMs, ABCs and IBPs recapitulating the role of KFs. A panel of histone/DNA methylation modifiers (HMMs) were revealed to bear potential value of relatively favorable prognosis in both adult and childhood patients. CONCLUSIONS We described the genome-wide abnormality patterns in adult B-ALL patients in comparison with those of pediatric cases, contributing to the understanding of leukemogenesis and the identification of potential new prognostic markers. Disclosures No relevant conflicts of interest to declare.
- Published
- 2014
17. The Complex Transcriptional Landscape of the Human Platelet
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Bray, Paul F., primary, McKenzie, Steven E., additional, Edelstein, Leonard C., additional, Nagalla, Srikanth, additional, Delgrosso, Kathleen, additional, Ertel, Adam, additional, Kupper, Joan, additional, Jing, Yi, additional, Londin, Eric R., additional, Loher, Phillipe, additional, Chen, Huang-Wen, additional, Fortina, Paolo M., additional, and Rigoutsos, Isidore, additional
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- 2012
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18. DNMT3A Mutation Leads to Hematopoietic Dysregulation.
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Xu, Jie, primary, Zhang, Wei-na, additional, Zhen, Tao, additional, Li, Yang, additional, Shi, Jing-yi, additional, Mi, Jian-qing, additional, Wang, Yue-ying, additional, Chen, Sai-juan, additional, and Chen, Zhu, additional
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- 2012
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19. Beyond mRNAs and Mirnas: Unraveling the Full-Spectrum of the Normal Human Platelet Transcriptome Through Next-Generation Sequencing
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Londin, Eric R., primary, Hatzimichael, Eleftheria, additional, Loher, Phillipe, additional, Zhao, Yue, additional, Jing, Yi, additional, Chen, Huang, additional, Edelstein, Leonard C., additional, Nagalla, Srikanth, additional, Delgrosso, Kathleen, additional, Ertel, Adam, additional, Kupper, Joan, additional, Fortina, Paolo M., additional, McKenzie, Steven E., additional, Bray, Paul F., additional, and Rigoutsos, Isidore, additional
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- 2012
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20. DNMT3A Mutation Leads to Hematopoietic Dysregulation
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Yue-Ying Wang, Tao Zhen, Jing-Yi Shi, Sai-Juan Chen, Zhu Chen, Jie Xu, Wei-Na Zhang, Jian-Qing Mi, and Yang Li
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Myeloid ,Immunology ,Mutant ,Cell Biology ,Hematology ,Transfection ,Biology ,Biochemistry ,Molecular biology ,Haematopoiesis ,medicine.anatomical_structure ,DNA methylation ,medicine ,Bone marrow ,Epigenetics ,Stem cell - Abstract
Abstract 2382 Epigenetic modification process is required for the development of hematopoietic cells. DNA methyltransferase DNMT3A, responsible for de novo DNA methylation, was newly reported to have a high frequency of mutations in hematopoietic malignancies. Conditional knock-out of DNMT3A promoted self-renewal activity of murine hematopoietic stem cells (HSCs). However, the role of mutated DNMT3A in hematopoiesis and its regulative mechanism of epigenetic network mostly remain unknown. Here we showed that the Arg882His (R882H) hotspot locus on DNMT3A impaired the normal function of this enzyme and resulted in an abnormal increase of primitive hematopoietic cells. In both controlled in vivo and in vitro assays, we found that the cells transfected by R882H mutant promoted cell proliferation, while decreased the differentiation of myeloid lineage compared to those with wild type. Analysis of bone marrow (BM) cells from mice transduced by R882H reveals an expansion of Lin−Sca-1+C-kit+ populations and a reduction of mature myeloid cells. Meanwhile, a cluster of upregulated genes and downregulated lineage-specific differentiation genes associated with hematopoiesis were discovered in mice BM cells with R882H mutation. We further evaluated the association of mutated DNMT3A and HOXB4 which was previously detected to be highly expressed in clinical samples carrying R882 mutation. Compared with wildtype DNMT3A, R882H mutation disrupted the repression of HOXB4 by largely recruiting tri-methylated histone 3 lysine 4 (H3K4). Taken together, our results showed that R882H mutation disturbed HSC activity through H3K4 tri-methylation, and transcriptional activation of HSC-related genes. Disclosures: No relevant conflicts of interest to declare.
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- 2012
21. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia
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Shen, Yang, primary, Zhu, Yong-Mei, additional, Fan, Xing, additional, Shi, Jing-Yi, additional, Wang, Qin-Rong, additional, Yan, Xiao-Jing, additional, Gu, Zhao-Hui, additional, Wang, Yan-Yan, additional, Chen, Bing, additional, Jiang, Chun-Lei, additional, Yan, Han, additional, Chen, Fei-Fei, additional, Chen, Hai-Min, additional, Chen, Zhu, additional, Jin, Jie, additional, and Chen, Sai-Juan, additional
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- 2011
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22. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets
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Wong, Kok Loon, primary, Tai, June Jing-Yi, additional, Wong, Wing-Cheong, additional, Han, Hao, additional, Sem, Xiaohui, additional, Yeap, Wei-Hseun, additional, Kourilsky, Philippe, additional, and Wong, Siew-Cheng, additional
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- 2011
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23. GATA-2 L359V Mutation Is Exclusively Associated with CML Progression but Not Other Hematological Malignancies and GATA-2 P250A Is a Novel Single Nucleotide Polymorphism.
- Author
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Zhang, Su-Jiang, primary, Shi, Jing-Yi, additional, and Li, Jianyong, additional
- Published
- 2009
- Full Text
- View/download PDF
24. GATA-2 L359V Mutation Is Solely Associated with Cml progression but Not Other Hematological Malignancies.
- Author
-
Zhang, Su-Jiang, primary and Shi, Jing-Yi, primary
- Published
- 2008
- Full Text
- View/download PDF
25. GATA-2 L359V Mutation Is Exclusively Associated with CML Progression but Not Other Hematological Malignancies and GATA-2 P250A Is a Novel Single Nucleotide Polymorphism
- Author
-
Jing-Yi Shi, Su-Jiang Zhang, and Jianyong Li
- Subjects
Mutation ,ABL ,Chronic lymphocytic leukemia ,Immunology ,breakpoint cluster region ,Myeloid leukemia ,Single-nucleotide polymorphism ,Cell Biology ,Hematology ,Biology ,medicine.disease_cause ,medicine.disease ,Biochemistry ,Myeloproliferative Disorders ,hemic and lymphatic diseases ,medicine ,Mutation testing - Abstract
Abstract 2187 Poster Board II-164 Chronic myeloid leukemia (CML) progression is characterized by occurrence of new cytogenetic and molecular abnormalities. In the previous study, we have shown the important role of GATA-2 L359V mutation in CML progression. To further ascertain the truth of transcription factor GATA-2 in hematological malignancies, we expanded our study to GATA-2 full length by directly sequencing and applied MassARRAY assay into GATA-2 L359V mutation analysis. Finally, no GATA-2 L359V mutation was found in 270 acute myeloid leukemia, 30 myelodysplastic syndrome, 50 acute lymphoblastic leukemia, 12 chronic lymphocytic leukemia, 40 CML chronic phase and 286 BCR/ABL negative myeloproliferative disorders except CML blast crisis. A new variation of GATA-2 resulted in P250A change was identified, which was not found to have statistical difference between patients with hematological malignancies and healthy control. Hence, we concluded GATA-2 L359V is exclusively associated with CML progression but not other hematological malignancies and P250A is a new single nucleotide polymorphism. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2009
26. Gain-of-Function Mutations of GATA-2 in Acute Myeloid Transformation of Chronic Myeloid Leukemia.
- Author
-
Zhang, Su-Jiang, primary, Ma, Li-Yuan, additional, Huang, Qiu-Hua, additional, Li, Guo, additional, Gu, Bai-Wei, additional, Gao, Xiao-Dong, additional, Shi, Jing-Yi, additional, Wang, Yue-Ying, additional, Gao, Li, additional, Cai, Xun, additional, Ren, Rui-Bao, additional, Chen, Zhu, additional, and Chen, Sai-Juan, additional
- Published
- 2007
- Full Text
- View/download PDF
27. Rituximab plus CHOP (R-CHOP) overcomes PRDM1-associated resistance to chemotherapy in patients with diffuse large B-cell lymphoma
- Author
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Liu, Yan-Yan, primary, Leboeuf, Christophe, additional, Shi, Jing-Yi, additional, Li, Jun-Min, additional, Wang, Li, additional, Shen, Yang, additional, Garcia, José-Francisco, additional, Shen, Zhi-Xiang, additional, Chen, Zhu, additional, Janin, Anne, additional, Chen, Sai-Juan, additional, and Zhao, Wei-Li, additional
- Published
- 2007
- Full Text
- View/download PDF
28. The Overall Analysis of JAK2 and MPL Mutation Status in Chinese MPD Patients by MassARRAY Assay
- Author
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Jianyong Li, Jun Xia, Su-Jiang Zhang, and Jing-Yi Shi
- Subjects
Oncology ,medicine.medical_specialty ,Pathology ,business.industry ,Sequence analysis ,Essential thrombocythemia ,Hypereosinophilic syndrome ,Immunology ,breakpoint cluster region ,Heterozygote advantage ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Polycythemia vera ,hemic and lymphatic diseases ,Internal medicine ,Mutation (genetic algorithm) ,Medicine ,business ,Myelofibrosis - Abstract
In recent three years the new notable progress associated with myeloproliferative disorder (MPD) was the identification of JAK2 and MPL mutations, which have been confirmed to be the major molecular mechanism and marker of BCR/ABL negative MPD. Multiple techniques including allele-specific PCR, conventional DNA sequencing, pyrosequencing as well as BsaXI restriction analysis have been used to detect these mutations. The previous data of Shanghai Group had demonstrated the sensitivity and preliminary result of JAK2 V617F in 162 Chinese patients with MPD using MassARRAY assay. To generally identify the frequency of these mutations in Chinese MPD patients, we continued to employ this technique-MassARRAY assay to detect JAK2 V617F, JAK2 K539L as well as MPL W515L mutation in a larger scale of Chinese MPD patients. A total of 204 Chinese MPD patients were enrolled in our study. These patients were referred to polycythemia vera (PV) (n=55), essential thrombocythemia (ET) (n=110), primary myelofibrosis (PMF) (n=29) and hypereosinophilic syndrome (HES) (n=10). 2 ml peripheral blood was obtained with informed consent and genomic DNA was isolated. The diagnosis of MPD was established according to the 2001 WHO diagnostic criteria. Finally, 187 patient samples with good signal can be analyzed for JAK2 V617F mutation. Among the available 101 signals of ET patients, 30 were heterozygous mutation and 9 were homozygous mutation. Among 52 PV patients, 25 were heterozygous mutation and 14 were homozygous mutation. Among 25 PMF patients, 9 were heterozygous mutation and 5 were homozygous mutation. None of HES patients was found harboring JAK2 V617F. In addition, we identified a PV patient harboring JAK2 K539L but not V617F mutation (1/52, 1.9%), and an ET patient harboring MPL W515L mutation (1/101, 1%). Both results were further confirmed by sequence analysis. Hence, we concluded that JAK2 V617F underlie the major molecular pathogenesis of Chinese MPD patients especially PV, however, JAK2 K539L and MPL W515L are rare events in these patients.
- Published
- 2008
29. GATA-2 L359V Mutation Is Solely Associated with Cml progression but Not Other Hematological Malignancies
- Author
-
Jing-Yi Shi and Su-Jiang Zhang
- Subjects
Mutation ,ABL ,Chronic lymphocytic leukemia ,Immunology ,breakpoint cluster region ,Hematopoietic stem cell ,Myeloid leukemia ,Cell Biology ,Hematology ,Disease ,Biology ,medicine.disease ,medicine.disease_cause ,Biochemistry ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Acute lymphocytic leukemia ,Cancer research ,medicine ,neoplasms - Abstract
Chronic Myeloid Leukemia (CML) is a hematopoietic stem cell disease with distinct biology and clinical features. According to clinical and biology process, CML can be divided as two different phase: the initial chronic phase (CP) and progression phase including accelerated phase (AP) followed by blast crisis (BC). In a previous study, we have identified the transcription factor GATA-2 L359V mutation in CML BC patients but not CP and its pivotal role in CML progression (PNAS 2008 105:2076–2081). Here, we continued to explore the occurrence of GATA-2 L359V mutation in other hematological malignancies using Mass-ARRAY assay and sequence analysis. A total of 652 patient samples were included in our study. These patients were referred to 270 Acute Myeloid Leukemia (AML) including M1–M7, 30 Myelodysplastic Syndrome (MDS), 50 Acute Lymphoblastic Leukemia (ALL), 12 Chronic Lymphocytic Leukemia (CLL), 40 CML CP and 250 BCR/ABL negative Myeloproliferative Disorder (MPD) patients. 5 ml bone marrow sample before therapy was collected with informed consent and genomic DNA was isolated. The diagnosis of AML, ALL, CML, CLL, MDS and MPD was established according to the 2001 WHO diagnostic criteria. In addition, 8 samples of CML BC harboring GATA-2 L359V were supplied into our study as positive control and 100 peripheral blood samples of healthy adult as normal control. As a result, no L359V mutation was detected in AML, ALL, MDS, CLL, BCR/ABL negative MPD and CML CP. Our data strongly suggested that GATA-2 L359V is solely associated with CML progression but not other hematological malignancies. Therefore, we favored this idea, i.e., BCR/ABL underlies the pathogenic basis of CML CP; However, subsequent genomic instabilities contribute to mutation of key transcription factor such as GATA-2 which ultimately trigger the blastic transformation of CML.
- Published
- 2008
30. Molecular Characterization of NRG Gene, a Novel Partner, Fused to NUP98 Gene as a Result of the t(3;11)(q29q13;p15) Translocation in an Acute Myeloid/T Lymphocytic Leukemia.
- Author
-
Chen, Sai-Juan, primary, Zhu, Yong-Jin, primary, Pan, Qin, primary, Gu, Bai-Wei, primary, Xie, Zhi-Yao, primary, Cai, Xun, primary, Pan, Jin-Lan, primary, Wu, Ya-Fang, primary, Shi, Jing-Yi, primary, Li, Guo, primary, Xiong, Shu-Min, primary, Xue, Yong-Quan, primary, and Chen, Zhu, primary
- Published
- 2005
- Full Text
- View/download PDF
31. Gain-of-Function Mutations of GATA-2 in Acute Myeloid Transformation of Chronic Myeloid Leukemia
- Author
-
Li Gao, Ruibao Ren, Guo Li, Liyuan Ma, Qiu-Hua Huang, Xun Cai, Jing-Yi Shi, Zhu Chen, Yue-Ying Wang, Bai-Wei Gu, Xiao-Dong Gao, Sai-Juan Chen, and Su-Jiang Zhang
- Subjects
Myeloid ,ABL ,Immunology ,breakpoint cluster region ,Myeloid leukemia ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Fusion gene ,Haematopoiesis ,Transactivation ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Cancer research ,medicine ,Progenitor cell - Abstract
Acquisition of additional genetic and/or epigenetic abnormalities other than BCR/ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast phase. To gain insights into the underlying mechanisms, we screened DNA samples from CML patients during acute transformation for alterations in a number of transcription factor genes crucial to myeloid-lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of GATA-2, a negative regulator of hematopoietic stem/progenitor cell differentiation. L359V within zinc finger domain (ZF) 2 of GATA-2 was found in 8 cases with myelo-monoblastic features, while an in-frame deletion of six amino acids (D341–346) across the border of ZF1 was detected in 1 patient at blast crisis with eosinophilia. Further studies showed that L359V not only increased transactivation activity, but also enhanced inhibitory effects on the major myelopoietic regulator PU.1. Consistent with the myelo-monoblastic features of CML patients with GATA-2 L359V mutant, transduction of GATA-2 L359V mutant into HL-60 cells or BCR/ABL-harboring mouse model disturbed myelo-monocytic differentiation/proliferation in vitro and in vivo, respectively. These data suggest that GATA-2 mutations may be involved in acute myeloid transformation in some CML patients.
- Published
- 2007
32. A Genomic and Proteomic Research for the Regulatory Networks of ATRA-Induced Differentiation of Acute Promyelocytic Leukemia Cells.
- Author
-
Huang, Qiu-Hua, primary, Zhang, Qun-Ye, primary, Shen, Shu-Hong, primary, Zheng, Pei-Zheng, primary, Lu, Jing, primary, Jing, Yi, primary, Zhang, Ji, primary, Wang, Kan-Kan, primary, Chen, Sai-Juan, primary, and Chen, Zhu, primary
- Published
- 2004
- Full Text
- View/download PDF
33. Molecular Characterization of NRG Gene, a Novel Partner, Fused to NUP98 Gene as a Result of the t(3;11)(q29q13;p15) Translocation in an Acute Myeloid/T Lymphocytic Leukemia
- Author
-
Sai-Juan Chen, Zhu Chen, Yong-Quan Xue, Shu-Min Xiong, Guo Li, Jing-Yi Shi, Ya-Fang Wu, Jin-Lan Pan, Xun Cai, Zhi-Yao Xie, Bai-Wei Gu, Qin Pan, and Yong-Jin Zhu
- Subjects
NUP98 Gene ,Immunology ,Chromosomal translocation ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Molecular biology ,Fusion gene ,Leukemia ,Exon ,Fusion transcript ,Transcriptional regulation ,medicine ,Gene - Abstract
The NUP98 gene has been reported to be fused with at least 17 partner genes in leukemia with 11p15 translocation. An adult patient with de novo acute myeloid/T lymphocytic leukemia harboring t(3;11)(q29q13;p15) has been investigated to characterize the genes involved in that translocation. Through molecular cytogenetic analysis, we identified a fusion transcript between NUP98 gene and a novel partner gene named as NUP98 related gene (NRG) at 3q29. Further molecular analysis showed that exon 13 of NUP98 was fused in-frame to exon 10 of NRG. Moreover, the segment from 3q13 to 3q29 translocated at 11p15 had been inverted and accompanied by the deletion of the distal portion of breakpoint at chromosome 3q29. Interestingly, the NUP98-NRG protein showed nuclear and cytoplasmic distribution, a pattern different from that of wild type NUP98 or NRG. When assayed in a GAL 4 reporter system, the fusion gene showed an aberrant trans-regulatory activity. Transfection in HL-60 cells demonstrated that NUP98-NRG could promote cell proliferation, survival and arrest differentiation. Therefore, NUP98-NRG may exert transforming effects by interfering with the cellular mechanism of transcriptional regulation. Our data provide thus new evidence that NUP98-related molecular abnormality is a recurrent genetic event in leukemogenesis.
- Published
- 2005
34. Exome Sequencing Identifies Somatic Mutations of DDX3Xin Natural Killer/T-Cell Lymphoma
- Author
-
Jiang, Lu, Gu, Zhao-Hui, Yan, Zi-Xun, Zhao, Xia, Xie, Yin-Yin, Zhang, Zi-Guan, Pan, Chun-Ming, Hu, Yuan, Cai, Chang-Ping, Dong, Ying, Wang, Li, Shen, Yang, Meng, Guoyu, Zhou, Jian-Feng, Hu, Jian-Da, Wang, Jin-Fen, Yang, Lin-Hua, Zhang, Feng, Wang, Jian-Min, Wang, Zhao, Peng, Zhi-Gang, Chen, Fang-Yuan, Sun, Zi-Min, Ding, Hao, Huang, Jin-Yan, Liu, Yuan-Hua, Shi, Jumei, Hou, Jian, Yan, Jin-Song, Shi, Jing-Yi, Xu, Lan, Li, Yang, Lu, Jing, Zheng, Zhong, Xue, Wen, Zhao, Wei-Li, Chen, Zhu, and Chen, Sai-Juan
- Abstract
Natural-killer/T cell lymphoma (NKTCL) is a malignant proliferation of CD56+/cytoCD3+ lymphocytes and constitutes a heterogeneous group of aggressive lymphoma prevalent in Asian and South American populations. NKTCL represents a distinct clinicopathologic entity of non-Hodgkin’s lymphoma, characterized by male predominance, strong association with Epstein-Barr virus (EBV) infection, prominent tissue necrosis and aggressive clinical course. However, molecular pathogenesis of NKTCL remains largely elusive.
- Published
- 2014
- Full Text
- View/download PDF
35. Gain-of-Function Mutations of GATA-2in Acute Myeloid Transformation of Chronic Myeloid Leukemia.
- Author
-
Zhang, Su-Jiang, Ma, Li-Yuan, Huang, Qiu-Hua, Li, Guo, Gu, Bai-Wei, Gao, Xiao-Dong, Shi, Jing-Yi, Wang, Yue-Ying, Gao, Li, Cai, Xun, Ren, Rui-Bao, Chen, Zhu, and Chen, Sai-Juan
- Abstract
Acquisition of additional genetic and/or epigenetic abnormalities other than BCR/ABL fusion gene is believed to cause disease progression in chronic myeloid leukemia (CML) from chronic phase to blast phase. To gain insights into the underlying mechanisms, we screened DNA samples from CML patients during acute transformation for alterations in a number of transcription factor genes crucial to myeloid-lymphoid development. In 85 cases of CML blast transformation, we identified two new mutations in the coding region of GATA-2, a negative regulator of hematopoietic stem/progenitor cell differentiation. L359V within zinc finger domain (ZF) 2 of GATA-2was found in 8 cases with myelo-monoblastic features, while an in-frame deletion of six amino acids (D341–346) across the border of ZF1 was detected in 1 patient at blast crisis with eosinophilia. Further studies showed that L359V not only increased transactivation activity, but also enhanced inhibitory effects on the major myelopoietic regulator PU.1. Consistent with the myelo-monoblastic features of CML patients with GATA-2L359V mutant, transduction of GATA-2L359V mutant into HL-60 cells or BCR/ABL-harboring mouse model disturbed myelo-monocytic differentiation/proliferation in vitroand in vivo, respectively. These data suggest that GATA-2mutations may be involved in acute myeloid transformation in some CML patients.
- Published
- 2007
- Full Text
- View/download PDF
36. Molecular Characterization of NRGGene, a Novel Partner, Fused to NUP98Gene as a Result of the t(3;11)(q29q13;p15) Translocation in an Acute Myeloid/T Lymphocytic Leukemia.
- Author
-
Chen, Sai-Juan, Zhu, Yong-Jin, Pan, Qin, Gu, Bai-Wei, Xie, Zhi-Yao, Cai, Xun, Pan, Jin-Lan, Wu, Ya-Fang, Shi, Jing-Yi, Li, Guo, Xiong, Shu-Min, Xue, Yong-Quan, Chen, Zhu, and Chen, Sai-Juan
- Abstract
The NUP98gene has been reported to be fused with at least 17 partner genes in leukemia with 11p15 translocation. An adult patient with de novoacute myeloid/T lymphocytic leukemia harboring t(3;11)(q29q13;p15) has been investigated to characterize the genes involved in that translocation. Through molecular cytogenetic analysis, we identified a fusion transcript between NUP98gene and a novel partner gene named as NUP98related gene (NRG)at 3q29. Further molecular analysis showed that exon 13 of NUP98was fused in-frame to exon 10 of NRG. Moreover, the segment from 3q13 to 3q29 translocated at 11p15 had been inverted and accompanied by the deletion of the distal portion of breakpoint at chromosome 3q29. Interestingly, the NUP98-NRGprotein showed nuclear and cytoplasmic distribution, a pattern different from that of wild type NUP98 or NRG. When assayed in a GAL 4 reporter system, the fusion gene showed an aberrant trans-regulatory activity. Transfection in HL-60 cells demonstrated that NUP98-NRG could promote cell proliferation, survival and arrest differentiation. Therefore, NUP98-NRG may exert transforming effects by interfering with the cellular mechanism of transcriptional regulation. Our data provide thus new evidence that NUP98-related molecular abnormality is a recurrent genetic event in leukemogenesis.
- Published
- 2005
- Full Text
- View/download PDF
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