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https://www.readbyqxmd.com/read/29778661/epigenetic-dysregulation-of-zeb1-is-involved-in-lmo2-promoted-t-cell-acute-lymphoblastic-leukaemia-leukaemogenesis
#1
Chao Wu, Jianjun Li, Chenchen Tian, Wen Shi, Huimin Jiang, Zhen Zhang, Hang Wang, Quansheng Zhang, Wei Sun, Peiqing Sun, Rong Xiang, Shuang Yang
T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29713515/the-role-of-tal1-in-hematopoiesis-and-leukemogenesis
#2
E R Vagapova, P V Spirin, T D Lebedev, V S Prassolov
TAL1 (SCL/TAL1, T-cell acute leukemia protein 1) is a transcription factor that is involved in the process of hematopoiesis and leukemogenesis. It participates in blood cell formation, forms mesoderm in early embryogenesis, and regulates hematopoiesis in adult organisms. TAL1 is essential in maintaining the multipotency of hematopoietic stem cells (HSC) and keeping them in quiescence (stage G0). TAL1 forms complexes with various transcription factors, regulating hematopoiesis (E2A/HEB, GATA1-3, LMO1-2, Ldb1, ETO2 , RUNX1, ERG, FLI1)...
January 2018: Acta Naturae
https://www.readbyqxmd.com/read/29561959/single-cell-qpcr-facilitates-the-optimization-of-hematopoietic-differentiation-in-hpscs-op9-coculture-system
#3
Haide Chen, Mengmeng Jiang, Lei Xiao, He Huang
Human pluripotent stem cells (hPSCs)/OP9 coculture system is a widely used hematopoietic differentiation approach. The limited understanding of this process leads to its low efficiency. Thus, we used single-cell qPCR to reveal the gene expression profiles of individual CD34+ cells from different stages of differentiation. According to the dynamic gene expression of hematopoietic transcription factors, we overexpressed specific hematopoietic transcription factors (Gata2, Lmo2, Etv2, ERG, and SCL) at an early stage of hematopoietic differentiation...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29555020/single-cell-transcriptomics-reveals-a-new-dynamical-function-of-transcription-factors-during-embryonic-hematopoiesis
#4
Isabelle Bergiers, Tallulah Andrews, Özge Vargel Bölükbaşı, Andreas Buness, Ewa Janosz, Natalia Lopez-Anguita, Kerstin Ganter, Kinga Kosim, Cemre Celen, Gülce Itır Perçin, Paul Collier, Bianka Baying, Vladimir Benes, Martin Hemberg, Christophe Lancrin
Recent advances in single-cell transcriptomics techniques have opened the door to the study of gene regulatory networks (GRNs) at the single-cell level. Here, we studied the GRNs controlling the emergence of hematopoietic stem and progenitor cells from mouse embryonic endothelium using a combination of single-cell transcriptome assays. We found that a heptad of transcription factors (Runx1, Gata2, Tal1, Fli1, Lyl1, Erg and Lmo2) is specifically co-expressed in an intermediate population expressing both endothelial and hematopoietic markers...
March 20, 2018: ELife
https://www.readbyqxmd.com/read/29507663/a-comprehensive-function-analysis-of-lmo2-in-different-breast-cancer-subtypes
#5
Ye Liu, Mei Yuan, Chao Wu, Tianhui Zhu, Wei Sun
Breast cancer is the most common invasive cancer in women worldwide, and can be subdivided into Luminal A, Luminal B, Her2, and Basal subtype (the PAM50 subtyping system). The lmo2 gene was traditionally recognized as a proto-oncogene in hematopoietic system but its functions in breast cancers remained largely unclear. Based on the Cancer Genome Atlas (TCGA) breast cancer dataset, herein we found that the significantly LMO2-correlated genes in normal or malignant samples were enriched in rather divergent cellular pathways, suggesting the function complexity of LMO2 in breast tissues...
February 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29456179/the-chromatin-remodeler-bptf-activates-a-stemness-gene-expression-program-essential-for-the-maintenance-of-adult-hematopoietic-stem-cells
#6
Bowen Xu, Ling Cai, Jason M Butler, Dongliang Chen, Xiongdong Lu, David F Allison, Rui Lu, Shahin Rafii, Joel S Parker, Deyou Zheng, Gang Greg Wang
Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29327714/a-comprehensive-flow-cytometry-based-immunophenotypic-characterization-of-burkitt-like-lymphoma-with-11q-aberration
#7
Grzegorz Rymkiewicz, Beata Grygalewicz, Magdalena Chechlinska, Katarzyna Blachnio, Zbigniew Bystydzienski, Joanna Romejko-Jarosinska, Renata Woroniecka, Michalina Zajdel, Katarzyna Domanska-Czyz, David Martin-Garcia, Ferran Nadeu, Pawel Swoboda, Jolanta Rygier, Barbara Pienkowska-Grela, Jan Konrad Siwicki, Monika Prochorec-Sobieszek, Itziar Salaverria, Reiner Siebert, Jan Walewski
We previously described a subset of MYC translocation-negative aggressive B-cell lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal losses in chromosome 11. In the 2016 WHO classification, these MYC-negative lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like lymphomas with 11q aberration. Cells were acquired by fine needle aspiration biopsy from 10 young adult patients, 80% of whom presented recurrence-free 5-year survival...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29309299/comparison-of-myocyte-enhancer-factor-2b-versus-other-germinal-center-associated-antigens-in-the-differential-diagnosis-of-b-cell-non-hodgkin-lymphomas
#8
Erika M Moore, Steven H Swerdlow, Sarah E Gibson
Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. We evaluated MEF2B expression, in comparison with additional GC markers, LIM domain-only transcription factor 2 (LMO2), and human GC-associated lymphoma (HGAL), in a variety of B-cell lymphomas, with particular emphasis on their utility in differentiating FL from MZL...
March 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29278703/overexpression-of-lhx2-suppresses-proliferation-of-human-t-cell-acute-lymphoblastic-leukemia-derived-cells-partly-by-reducing-lmo2-protein-levels
#9
Kazuya Miyashita, Kenji Kitajima, Susumu Goyama, Toshio Kitamura, Takahiko Hara
T cell acute lymphoblastic leukemia (T-ALL) is a malignant cancer with poor prognosis. The transcriptional co-factor LIM domain only 2 (LMO2) and its target gene HHEX are essential for self-renewal of T cell precursors and T-ALL etiology. LMO2 directly associates with LDB1 in a large DNA-containing nuclear complex and controls the transcription of T-ALL-related genes. Recently, we reported that overexpression of the LIM-homeodomain transcription factor, Lhx2, results in liberation of the Lmo2 protein from the Lmo2-Ldb1 complex, followed by ubiquitin proteasome mediated degradation...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29141987/brachyury-directs-histone-acetylation-to-target-loci-during-mesoderm-development
#10
Arica Beisaw, Pavel Tsaytler, Frederic Koch, Sandra U Schmitz, Maria-Theodora Melissari, Anna D Senft, Lars Wittler, Tracie Pennimpede, Karol Macura, Bernhard G Herrmann, Phillip Grote
T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (TY88A ) results in decreased histone 3 lysine 27 acetylation (H3K27ac) at T target sites, including the T locus, suggesting that T autoregulates the maintenance of its expression and functions by recruiting permissive chromatin modifications to putative enhancers during mesoderm specification...
January 2018: EMBO Reports
https://www.readbyqxmd.com/read/29140403/klhl6-is-preferentially-expressed-in-germinal-center-derived-b-cell-lymphomas
#11
Christian A Kunder, Giovanna Roncador, Ranjana H Advani, Gabriela Gualco, Carlos E Bacchi, Jean M Sabile, Izidore S Lossos, Kexin Nie, Robert John Tibshirani, Michael R Green, Ash A Alizadeh, Yasodha Natkunam
Objectives: KLHL6 is a recently described BTB-Kelch protein with selective expression in lymphoid tissues and is most strongly expressed in germinal center B cells. Methods: Using gene expression profiling as well as immunohistochemistry with an anti-KLHL6 monoclonal antibody, we have characterized the expression of this molecule in normal and neoplastic tissues. Protein expression was evaluated in 1,058 hematopoietic neoplasms. Results: Consistent with its discovery as a germinal center marker, KLHL6 was positive mainly in B-cell neoplasms of germinal center derivation, including 95% of follicular lymphomas (106/112)...
November 20, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29097500/a-bioclinical-prognostic-model-using-myc-and-bcl2-predicts-outcome-in-relapsed-refractory-diffuse-large-b-cell-lymphoma
#12
Mark Bosch, Ariz Akhter, Bingshu E Chen, Adnan Mansoor, David Lebrun, David Good, Michael Crump, Lois Shepherd, David W Scott, Douglas A Stewart
The objective of this study was to create a bioclinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group (CCTG) LY12 prospective study. In 91 cases, sufficient histologic material was available to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and phosphoSTAT3 (pySTAT3) expression. Sixty-seven cases had material sufficient for fluorescent in situ hybridization (FISH) for MYC and BCL2 In addition, 97 formalin-fixed, paraffin-embedded tissue samples underwent digital gene expression profiling (GEP) to evaluate BCL2, MYC, P53 , and STAT3 expression, and to determine cell-of-origin (COO) using the Lymph2Cx assay...
February 2018: Haematologica
https://www.readbyqxmd.com/read/29046446/foamy-virus-vector-carries-a-strong-insulator-in-its-long-terminal-repeat-which-reduces-its-genotoxic-potential
#13
Michael Aaron Goodman, Paritha Arumugam, Devin Marie Pillis, Anastacia Loberg, Mohammed Nasimuzzaman, Danielle Lynn, Johannes Christiaan Maria van der Loo, Phillip Joseph Dexheimer, Mehdi Keddache, Thomas Roy Bauer, Dennis Durand Hickstein, David William Russell, Punam Malik
Strong viral enhancers in gammaretrovirus vectors have caused cellular proto-oncogene activation and leukemia, necessitating the use of cellular promoters in "enhancerless" self-inactivating integrating vectors. However, cellular promoters result in relatively low transgene expression, often leading to inadequate disease phenotype correction. Vectors derived from foamy virus, a nonpathogenic retrovirus, show higher preference for nongenic integrations than gammaretroviruses/lentiviruses and preferential integration near transcriptional start sites, like gammaretroviruses...
January 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29034206/leukemia-initiating-cells-in-t-cell-acute-lymphoblastic-leukemia
#14
REVIEW
Shi Hao Tan, Fatima Carla Bertulfo, Takaomi Sanda
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy characterized by the clonal proliferation of immature T-cell precursors. T-ALL has many similar pathophysiological features to acute myeloid leukemia, which has been extensively studied in the establishment of the cancer stem cell (CSC) theory, but the CSC concept in T-ALL is still debatable. Although leukemia-initiating cells (LICs), which can generate leukemia in a xenograft setting, have been found in both human T-ALL patients and animal models, the nature and origin of LICs are largely unknown...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28994199/inhibition-of-mek-erk-signalling-pathway-promotes-erythroid-differentiation-and-reduces-hscs-engraftment-in-ex-vivo-expanded-haematopoietic-stem-cells
#15
Morteza Zarrabi, Elaheh Afzal, Mohammad Hossein Asghari, Monireh Mohammad, Hamidreza Aboulkheyr Es, Marzieh Ebrahimi
The MEK/ERK pathway is found to be important in regulating different biological processes such as proliferation, differentiation and survival in a wide variety of cells. However, its role in self-renewal of haematopoietic stem cells is controversial and remains to be clarified. The aim of this study was to understand the role of MEK/ERK pathway in ex vivo expansion of mononuclear cells (MNCs) and purified CD34+ cells, both derived from human umbilical cord blood (hUCB). Based on our results, culturing the cells in the presence of an inhibitor of MEK/ERK pathway-PD0325901 (PD)-significantly reduces the expansion of CD34+ and CD34+  CD38- cells, while there is no change in the expression of stemness-related genes (HOXB4, BMI1)...
March 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28973433/lmo2-is-required-for-tal1-dna-binding-activity-and-initiation-of-definitive-haematopoiesis-at-the-haemangioblast-stage
#16
Vesna S Stanulovic, Pierre Cauchy, Salam A Assi, Maarten Hoogenkamp
LMO2 is a bridging factor within a DNA binding complex and is required for definitive haematopoiesis to occur. The developmental stage of the block in haematopoietic specification is not known. We show that Lmo2-/- mouse embryonic stem cells differentiated to Flk-1+ haemangioblasts, but less efficiently to haemogenic endothelium, which only produced primitive haematopoietic progenitors. Genome-wide approaches indicated that LMO2 is required at the haemangioblast stage to position the TAL1/LMO2/LDB1 complex to regulatory elements that are important for the establishment of the haematopoietic developmental program...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28954807/lmo2-lim-domain-only-2-and-endothelial-cell-migration-in-developmental-and-postnatal-angiogenesis
#17
EDITORIAL
Vijay Chaitanya Ganta, Brian H Annex
No abstract text is available yet for this article.
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28946938/ldb2-regulates-the-expression-of-dll4-through-the-formation-of-oligomeric-complexes-in-endothelial-cells
#18
Hyun-Jung Choi, Seung-Sik Rho, Dong-Hoon Choi, Young-Guen Kwon
Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish...
January 2018: BMB Reports
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#19
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T-cell acute lymphoblastic leukemia (T-ALL) patients, and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA-binding Runt domain and are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T-cell transformation. RUNX1 has been proposed to have tumor suppressor roles in T-cell leukemia homeobox 1/3-transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet, retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
October 12, 2017: Blood
https://www.readbyqxmd.com/read/28775072/lmo2-lim-domain-only-2-modulates-sphk1-sphingosine-kinase-and-promotes-endothelial-cell-migration
#20
Gianfranco Matrone, Shu Meng, Qilin Gu, Jie Lv, Longhou Fang, Kaifu Chen, John P Cooke
OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) (y1) zebrafish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1...
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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