scholarly journals Prognostic Significance ofNOTCH1andFBXW7Mutations in Pediatric T-ALL

2010 ◽  
Vol 28 (6) ◽  
pp. 353-360 ◽  
Author(s):  
Yucel Erbilgin ◽  
Muge Sayitoglu ◽  
Ozden Hatirnaz ◽  
Omer Dogru ◽  
Arzu Akcay ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Notch Signaling ◽  
B Lymphocyte ◽  
Prognostic Significance ◽  
Notch Signaling Pathway ◽  
Biological Data ◽  
Multicellular Organisms ◽  
Relationship Of ◽  
The Relationship

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment.NOTCH1and FBXW7 mutations both lead the activation of theNOTCH1pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis ofNOTCH1andFBXW7genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activatingNOTCH1mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had bothNOTCH1andFBXW7mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients.NOTCH1andFBXW7,NOTCH1alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However,NOTCH1andFBXW7mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.

scholarly journals Notch Signaling in T-Cell Development and T-ALL

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoyu Li ◽  
Harald von Boehmer
Keyword(s):  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Notch Signaling Pathway ◽  
Lineage Specification ◽  
Evolutionarily Conserved ◽  
Multiple Levels ◽  
Multicellular Organisms ◽  
T Cell Maturation

The Notch signaling pathway is an evolutionarily conserved cell signaling system present in most multicellular organisms, as it controls cell fate specification by regulating cell proliferation, differentiation, apoptosis, and survival. Regulation of the Notch signaling pathway can be achieved at multiple levels. Notch proteins are involved in lineage fate decisions in a variety of tissues in various species. Notch is essential for T lineage cell differentiation including T versus B and αβ versus γδ lineage specification. In this paper, we discuss Notch signaling in normal T-cell maturation and differentiation as well as in T-cell acute lymphoblastic lymphoma/leukemia.

scholarly journals Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion

2007 ◽  
Vol 204 (3) ◽  
pp. 645-655 ◽  
Author(s):  
Menno C. van Zelm ◽  
Tomasz Szczepański ◽  
Mirjam van der Burg ◽  
Jacques J.M. van Dongen
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Expansion ◽  
B Lymphocyte ◽  
Somatic Hypermutation ◽  
Homeostatic Proliferation ◽  
History Of ◽  
Lymphocyte Homeostasis

The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.

Analysis of the Relationship Between Notch Signaling Pathway and CDx2 Expression in the Development of Barrett's Esophagus

2011 ◽  
Vol 140 (5) ◽  
pp. S-307
Author(s):  
Yuji Tamagawa ◽  
Norihisa Ishimura ◽  
Goichi Uno ◽  
Takafumi Yuki ◽  
Hideaki Kazumori ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Notch Signaling Pathway ◽  
Cdx2 Expression ◽  
The Relationship

scholarly journals Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells

Oncogene ◽  
2019 ◽  
Vol 39 (6) ◽  
pp. 1185-1197 ◽  
Author(s):  
Mónica López-Guerra ◽  
Sílvia Xargay-Torrent ◽  
Patricia Fuentes ◽  
Jocabed Roldán ◽  
Blanca González-Farré ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Notch Signaling Pathway ◽  
Lymphocytic Leukemia ◽  
Therapeutic Targeting ◽  
Notch Ligand

Abstract Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly in NOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling in NOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both in NOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-induced MYC, CCND1, and NPM1 gene expression as well as cell proliferation in NOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such as CXCR4, NRARP, and VEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation in NOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients.

scholarly journals The Notch signaling pathway controls CD8+ T cell differentiation independently of the classical effector HES1

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215012 ◽  
Author(s):  
Dave Maurice De Sousa ◽  
Frédéric Duval ◽  
Jean-François Daudelin ◽  
Salix Boulet ◽  
Nathalie Labrecque
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cd8 T Cell ◽  
Notch Signaling Pathway ◽  
T Cell Differentiation

scholarly journals SPON2 Is Upregulated through Notch Signaling Pathway and Promotes Tumor Progression in Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1439
Author(s):  
Hyeon-Gu Kang ◽  
Won-Jin Kim ◽  
Myung-Giun Noh ◽  
Kyung-Hee Chun ◽  
Seok-Jun Kim
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Notch Signaling Pathway ◽  
Migration And Invasion ◽  
Gene Assay ◽  
Gastric Cancer Progression

Spondin-2 (SPON2) is involved in cancer progression and metastasis of many tumors; however, its role and underlying mechanism in gastric cancer are still obscure. In this study, we investigated the role of SPON2 and related signaling pathway in gastric cancer progression and metastasis. SPON2 expression levels were found to be upregulated in gastric cancer cell lines and patient tissues compared to normal gastric epithelial cells and normal controls. Furthermore, SPON2 silencing was observed to decrease cell proliferation and motility and reduce tumor growth in xenograft mice. Conversely, SPON2 overexpression was found to increase cell proliferation and motility. Subsequently, we focused on regulatory mechanism of SPON2 in gastric cancer. cDNA microarray and in vitro study showed that Notch signaling is significantly correlated to SPON2 expression. Therefore, we confirmed how Notch signaling pathway regulate SPON2 expression using Notch signaling-related transcription factor interaction and reporter gene assay. Additionally, activation of Notch signaling was observed to increase cell proliferation, migration, and invasion through SPON2 expression. Our study demonstrated that Notch signaling-mediated SPON2 upregulation is associated with aggressive progression of gastric cancer. In conclusion, we suggest upregulated SPON2 via Notch signaling as a potential target gene to inhibit gastric cancer progression.

scholarly journals The Notch Signaling Pathway Controls Short-Lived Effector CD8+ T Cell Differentiation but Is Dispensable for Memory Generation

2015 ◽  
Vol 194 (12) ◽  
pp. 5654-5662 ◽  
Author(s):  
Mélissa Mathieu ◽  
Frédéric Duval ◽  
Jean-François Daudelin ◽  
Nathalie Labrecque
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cd8 T Cell ◽  
Notch Signaling Pathway ◽  
T Cell Differentiation
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